Medical genetics
Omentin serum levels and omentin gene Val109Asp polymorphism in patients with psoriasis Hakan Turan1, Kursat Oguz Yaykasli2, Hatice Soguktas2, Emine Yaykasli2, Msc, Cihangir Aliagaoglu1, Teoman Erdem3, Mutlu Karkucak4, Ertugrul Kaya5, Taner Ucgun6, and Anzel Bahadir7
Departments of1 Dermatology, Duzce University Medical Faculty, 2Medical Genetics, Duzce University Medical Faculty, 3 Dermatology, Sakarya University Education and Research Hospital, 4 Medical Genetics, Sakarya University Education and Research Hospital, 5 Pharmacology, Duzce University Medical Faculty, 6Biochemistry, Duzce University Medical Faculty, and 7Biophysics, Duzce University Medical Faculty, Duzce, Turkey
Abstract Background Psoriasis is a chronic inflammatory disease of uncertain pathogenesis. Omentin is a new adipokine with anti-inflammatory properties; however, the relationship between psoriasis and omentin has not been fully established yet. Objectives This study was designed to evaluate the relationship between psoriasis and omentin serum levels and Val109Asp polymorphism in exon 4 of the omentin gene. Methods Forty-nine patients with plaque-type psoriasis and 39 healthy subjects were included in the study. Omentin concentrations were determined by using enzyme-linked immunosorbent assay. Val109Asp polymorphism in exon 4 of the omentin gene was assessed by the polymerase chain reaction–restriction fragment length polymorphism
Correspondence Dr. Hakan Turan, Assistant Professor Department of Dermatology Duzce University Medical Faculty Konuralp 81000 Duzce Turkey E-mail: [email protected] Conflict of interest: None declared. doi: 10.1111/ijd.12306
method. Genotypes were determined according to the bands formed in agarose electrophoresis gels. In the statistical analysis, the level of significance was set at P < 0.05. Results The serum omentin levels of the patients with psoriasis (354.2 152.0) were found to be significantly lower than those in the control group (488.7 190.3) (P = 0.001). A moderate level negative correlation was determined between serum omentin level and body mass index and waist circumference. No significant differences were observed between the patient and control groups in terms of the genotype and allele frequency of Val109Asp polymorphism in exon 4 of the omentin gene (P > 0.05). Conclusions Omentin serum levels were determined to be low in patients with psoriasis. No significant difference was found regarding Val109Asp polymorphism of the omentin gene. To the best of our knowledge, our study is the first clinical study to examine the relationship between psoriasis and omentin in terms of serum and genomic levels.
Introduction Psoriasis is a chronic, relapsing inflammatory disease with a heterogeneous genetic background that affects approximately 1–3% of the Caucasian population. The pathogenesis of psoriasis is still unknown. Adipose tissue is a metabolically active organ that releases various bioactive peptides known as adipokines, which contribute to the regulation of vital functions, such as insulin-mediated processes, lipid and glucose metabolism, vascular changes, and inflammation.1,2 Omentin, a new adipokine secreted by the stromal vascular cells of visceral adipose tissue,3 is considered associated with vascular, metabolic, and various chronic inflammatory diseases.4–7 There is currently only one study in the ª 2013 The International Society of Dermatology
literature that examines the relationship between psoriasis and serum omentin levels.8 The human omentin gene consists of eight exons and seven introns located on chromosome 1q21.39. To our knowledge, the literature includes only one study on omentin gene polymorphism. Sch€ affler et al.4 examined Val109Asp polymorphism in exon 4 of the omentin gene in type 2 diabetes and chronic inflammatory bowel disease. This polymorphism was investigated in relation to clinical parameters and in terms of the impact of pathogenesis; the effect of polymorphism on the omentin serum levels was not examined. The objective of this study was to compare the serum omentin levels of patients with psoriasis and control groups and to assess the role of Val109Asp polymorphism International Journal of Dermatology 2013
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Omentin levels and polymorphism in psoriasis
of the omentin gene in the pathogenesis of psoriasis and its effect on omentin levels.
CTCTCCTTCTTCTCCAGCCCAT-3′.10 PCR primers for codon 109 were used to generate a 471 bp product containing the polymorphic sites. The PCR products were digested with the
Materials and Methods Study subjects A total of 49 patients with plaque-type psoriasis who presented to our outpatient clinic between May 2011 and July 2012, as well as 39 healthy controls, were included in the study. Approval for the study was obtained from the local ethics committee. All participants gave their written informed consent for participation in the medical research, and the investigations were conducted in accordance with the principles of the Declaration of Helsinki. The study exclusion criteria included the administration of any systemic treatment in the previous six months and topical treatment in the previous month, psoriatic arthritis, metabolic syndrome and metabolic risk, diabetes mellitus, polycystic ovary syndrome, hepatic and renal disease, malignancy, smoking, and the use of chronic medication. The age, sex, waist circumference, height, weight, and body mass index (BMI) of all the participants were recorded. In addition, disease duration and psoriasis area severity index (PASI) of the participants in the patient group were measured. Clinical and laboratory measurements Body mass index was calculated as kg/m2, and all participants were classified as normal weight (18–25), overweight (25–30), or obese (>30). Waist circumference was measured at the midpoint between the lower border of the rib cage and the iliac crest. Psoriasis was evaluated as mild (PASI 12). Metabolic syndrome was assessed according to the US National Cholesterol Education Program Adult Treatment Panel III guidelines.9 All blood samples were collected in the morning after a 12-hour overnight fast. Within 15 minutes after collection, the blood samples were centrifuged at 2.750 g for 10 minutes. The supernatant part was transferred to polypropylene tubes and stored at –80 °C until analysis. Serum omentin levels were assessed using a commercial enzyme-linked immunosorbent assay kit (Bio Vendor, Brno, Czech Republic). DNA extraction and genotyping of omentin (Val109Asp) Blood samples were obtained from the patient and control groups and collected in EDTA tubes. Genomic DNA was extracted from whole blood using a DNA isolation kit (PureLink; Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s instructions, and the samples were stored at –20 °C until analysis by the polymerase chain reaction (PCR)–restriction fragment length polymorphism method. The genotype at the omentin gene Val109Asp polymorphism was determined using the PCR–restriction fragment length polymorphism method by the following primers: forward 5′GAGCCTTTAGGCCATGTCTCT-3′ and reverse 5′International Journal of Dermatology 2013
restriction enzymes AccI (NEB, Hitchin, Herts, UK) at 37 °C for 16 hours and analyzed on a 3% agarose gel. Val/Val individuals had 274 bp and 197 bp fragments; Val/Asp individuals had 471 bp, 274 bp, and 197 bp fragments; and Asp/Asp individuals had only a 471 bp fragment.
Statistical analysis Statistical analyses were performed using PASW 18 statistical software (ver. 18.0 for Windows; SPSS Inc., Chicago, IL, USA). Normality analyses of continuous variables were performed with histogram curves. Continuous variables were presented as mean SD, and independent samples t tests and Mann– Whitney U tests were used when comparing the two groups. Spearman’s test was performed for determining linear correlations between serum omentin levels and waist circumference, BMI, disease duration, and PASI scores. Genotype and allele frequencies were compared by using a chisquared test, and the results were presented as frequency and percentage. P < 0.05 was considered statistically significant.
Results Clinical and demographic characteristics of the patient and control groups are summarized in Table 1. There were no differences between the two groups in terms of age, sex, BMI, or waist circumference. PASI scores were between 1 and 26, with an average of 5.02 5.38 (mean SD). According to PASI score severity, 42 patients were in the mild severity group, and seven patients were in the moderate and severe groups. Psoriasis disease duration was 1–40 years, with a mean value of 11.54 9.99 (mean SD). Serum omentin levels were found to be significantly lower (P = 0.001) in the patients with psoriasis (354.2 152.0) compared to the control group (488.7 190.3). The serum omentin levels of patients with mild and moderate–severe psoriasis were Table 1 Clinical and demographic characteristics of the patient group and control group
Parameters Gender, male/female Age (years SD) Waist circumferences (cm SD) BMI (kg/m2 SD) PASI Disease duration (year) Omentin, ng/mL
Patient group n = 49
Control group n = 39
P value
23/26 37.4 15.2 90.7 5.35
20/19 32.8 7.1 86.05 12.16
NS NS NS
25.02 3.2 N/A N/A 488.7 190.3
NS N/A N/A 0.001
26.5 5.02 11.54 354.2
5.7 5.38 9.99 152.0
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Omentin levels and polymorphism in psoriasis
357.2 146.3 and 336.6 194.7, respectively, with no statistically significant difference (P > 0.05). A significant relationship and a moderate negative correlation were detected between serum omentin levels and BMI in the patient (P = 0.02, r = –0.447) and control (P = 0.04, r = –0.421) groups. In addition, there was a significant relationship and a moderate negative correlation between serum omentin levels and waist circumference in the patient (P = 0.013, r = – 0.463) and control (P = 0.018, r = – 0.417) groups. No significant relationship was found between serum omentin levels and disease duration or between serum omentin levels and PASI score. When omentin gene Val109Asp polymorphism was investigated, it was observed that 33 patients (67%) in the psoriasis group had Asp/Asp genotype, 14 (29%) had Asp/Val genotype, and two (4%) had Val/Val genotype. In the control group, 25 (64%) had Asp/Asp genotype, 11 (28%) had Asp/Val genotype, and three (8%) had Val/ Val genotype. Regarding genotype distribution, no statistical significance was determined between the patients with psoriasis and the control group (P > 0.05) (Table 2). Regarding omentin gene Val109Asp polymorphism, the frequency of the polymorphic Val allele was observed to be 18% in the patient group and 22% in the control group. No statistical significance was determined, although the Val allele was high in the patients with psoriasis group (Table 2). Discussion In this study, serum omentin levels and Val109Asp polymorphism in the omentin gene were investigated in patients with psoriasis. Serum omentin levels were lower in the patients with psoriasis compared to the control group. However, there were no significant differences between the patient and control groups in terms of the genotype and allele frequency of Val109Asp polymorphism in the omentin gene. To our knowledge, our study is the first clinical study in the literature to examine the relationship between psoriasis and omentin in terms of serum and genomic levels. Table 2 The distribution of genotypes in the patient group and control group Variables
Patient group n = 49
Genotypes Asp/Asp 33 (67%) Asp/Val 14 (29%) Val/Val 2 (4%) Frequency of alleles Asp 82% Val 18%
Control group n = 39
P value
25 (64%) 11 (28%) 3 (8%)
0.926 0.841 0.651
78% 22%
0.595
ª 2013 The International Society of Dermatology
Medical genetics
As the immunological basis of psoriasis has been understood better in recent years, it has been noted with greater emphasis that psoriasis is not limited to the skin but that it is a systemic disease with various comorbidities. Patients with psoriasis carry a high risk of comorbidities such as vascular diseases and metabolic syndrome.11 Chronic inflammation is known to be the main pathological process that causes skin involvement and comorbidities in psoriasis. Adipokines secreted by the adipose tissue are proteins that regulate nutrient metabolism, immune response, and inflammation.12 Omentin is an adipokine first discovered in 2003 and identified from visceral omental fat tissue.13 It has been reported that serum omentin levels significantly decrease in obesity, polycystic ovary syndrome, atherosclerosis, and diabetes, and that it is negatively correlated with risk factors such as high body mass index, waist circumference, and insulin resistance.8,14,15 Omentin also has an anti-inflammatory effect that works through the nuclear factor (NF) jb route16. NF-jB is a potent proinflammatory transcription factor responsible for the onset and amplification of the inflammatory response.17 Activation and DNA binding of NF-jB because of the degradation of inhibitory proteins (IkBa) induce the transcription of target genes responsible for immune response and inflammatory functions.18 In recent years, there has been evidence that NF-jB plays a role in the pathogenesis of psoriasis and other inflammatory diseases.19–21 Zhong et al.16 have shown that omentin inhibits tumor necrosis factor a-induced IkBa degradation and NF-jB activity in human umbilical vein endothelial cells. This information suggests that omentin may be closely associated with psoriasis pathogenesis via NF-jB inhibition. The biological effects of omentin on psoriasis and the effects of serum levels and psoriasis on omentin levels have not yet been fully understood. There is currently a single study on the relationship between psoriasis and omentin. Ismail and Mohamed8 investigated the relationship of serum omentin levels with disease duration and severity and obesity markers in patients with psoriasis and concluded that serum omentin levels were significantly lower in the psoriasis group compared to the control group (with no difference in waist circumference and BMI). In their study, exclusion criteria included the factors that affected omentin serum levels. Consequently, BMI and waist circumference and serum omentin levels were negatively correlated. No relationship was found between the duration and severity of disease and omentin serum levels. It was suggested that the low serum omentin levels could have contributed to the increased prevalence of cardiovascular diseases in patients with psoriasis. However, considering the exclusion criteria of the study and International Journal of Dermatology 2013
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the absence of any difference between obesity markers of the two groups, no comment was made on why omentin serum levels were lower in patients with psoriasis. In our study, similar to the results obtained by Ismail and Mohamed,8 omentin levels were found to be lower in patients with psoriasis once the parameters that could affect the omentin serum levels were excluded. This result has led us to consider that low omentin levels might contribute to the pathogenesis of both psoriasis and accompanying cardiovascular and metabolic diseases by triggering inflammation. We determined a negative correlation at moderate level between serum omentin levels and BMI and waist circumference in both the patient and control groups. We were unable to find any relationship between omentin serum levels and disease duration or PASI score. Although a numeric difference was observed between the serum omentin levels of mild (357.2 146.3) and moderate–severe (336.6 194.7) patients, there was no statistical difference. This result may be explained by the low number of patients in the moderate–severe group. There are studies in literature that suggest that gene polymorphism might affect the production, activity, and level of the product.22–24 As such, we considered that a possible polymorphism in the omentin gene might affect serum omentin levels. Sch€affler et al.10 investigated the relationships between Val109Asp polymorphism of omentin gene and type 2 diabetes mellitus, ulcerative colitis, and Crohn’s disease, in which omentin may have a pathogenic role; however, they found no significant relationship between the diseases and the genotype. In this study, we also evaluated the effects of omentin Val109Asp polymorphism on omentin serum levels and disease pathogenesis. Despite the high rate of Val allele frequency in the patient group, no statistical differences were detected between the groups in terms of genotype and allele frequency. We are of the opinion that the low omentin levels in the patient group might not be associated with Val109Asp polymorphism but may have resulted from another polymorphism in the gene or other factors that have not been determined yet. Similar to the previous study, omentin serum levels were found to be lower in the patient group compared to the control group. When the omentin gene was examined with regard to Val109Asp polymorphism, no difference was determined between the patient and control groups; thus, it was concluded that this polymorphism had no effect on omentin serum levels. In our study, although the sample size is not too small overall, it might be inadequate for the subcategories. Therefore, the results obtained in this study should be supported by other studies conducted with larger patient groups and by assessing other gene polymorphisms. International Journal of Dermatology 2013
Acknowledgments This study was supported by the Duzce University Scientific Research Projects Commission (project no. 2011.04.03.082). References 1 Guerre-Millo M. Adipose tissue and adipokines: for better or worse. Diabetes Metab 2004; 30: 13–19. 2 Ronti T, Lupattelli G, Mannarino E. The endocrine function of adipose tissue: an update. Clin Endocrinol (Oxf) 2006; 64: 355–365. 3 Wang Y, Lam KS, Kraegen EW, et al. Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem 2007; 53: 34–41. 4 Sch€ affler A, Zeitoun M, Wobser H. Frequency and significance of the novel single nucleotide missense polymorphism Val109Asp in the human gene encoding omentin in Caucasian patients with type 2 diabetes mellitus or chronic inflammatory bowel diseases. Cardiovasc Diabetol 2007; 6: 3. 5 Senolt L, Polansk a M, Filkov a M, et al. Vaspin and omentin: new adipokines differentially regulated at the site of inflammation in rheumatoid arthritis. Ann Rheum Dis 2010; 69: 1410–1411. 6 Shibata R, Ouchi N, Kikuchi R, et al. Circulating omentin is associated with coronary artery disease in men. Atherosclerosis 2011; 219: 811–814. 7 Pan HY, Guo L, Li Q. Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes. Diabetes Res Clin Pract 2010; 88: 29–33. 8 Ismail SA, Mohamed SA. Serum levels of visfatin and omentin-1 in patients with psoriasis and their relation to disease severity. Br J Dermatol 2012; 167: 436–439. 9 National Cholesterol Education Program (NCEP); Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation 2002; 106: 3143–3421. 10 Sch€ affler A, Neumeier M, Herfarth H, et al. Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue. Biochim Biophys Acta 2005; 1732: 96–102. 11 Gerdes S, Mrowietz U. Impact of comorbidities on the management of psoriasis. Curr Probl Dermatol 2009; 38: 21–36. 12 Hida K, Wada J, Zhang H, et al. Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats. J Lipid Res 2000; 41: 1615–1622. ª 2013 The International Society of Dermatology
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13 Yang R, Xu A, Pray J, et al. Cloning of omentin a new adipocytokine from omental fat tissue in humans. Diabetes 2003; (Suppl 1): A1. 14 de Souza Batista CM, Yang RZ, Lee MJ, et al. Omentin plasma levels and gene expression are decreased in obesity. Diabetes 2007; 56: 1655–1661. 15 Tan BK, Adya R, Farhatullah S, et al. Omentin-1, a novel adipokine, is decreased in overweight insulin-resistant women with polycystic ovary syndrome: ex vivo and in vivo regulation of omentin-1 by insulin and glucose. Diabetes 2008; 57: 801–808. 16 Zhong X, Li X, Liu F, et al. Omentin inhibits TNF-a-induced expression of adhesion molecules in endothelial cells via ERK/NF-jB pathway. Biochem Biophys Res Commun 2012; 425: 401–406. 17 Kwak JH, Jung JK, Lee H. Nuclear factor-kappa B inhibitors; a patent review (2006–2010). Expert Opin Ther Pat 2011; 21: 1897–1910. 18 Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 1999; 18: 6853–6866. 19 Doger FK, Dikicioglu E, Ergin F, et al. Nature of cell kinetics in psoriatic epidermis. J Cutan Pathol 2007; 34: 257–263.
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Medical genetics
20 Marchetti S, Gamas P, Belhacene N, et al. The caspase-cleaved form of LYN mediates a psoriasis-like inflammatory syndrome in mice. EMBO J 2009; 28: 2449–2460. 21 Lizzul PF, Aphale A, Malaviya R. Differential expression of phosphorylated NF-kappaB/RelA in normal and psoriatic epidermis and downregulation of NF-kappaB in response to treatment with etanercept. J Invest Dermatol 2005; 124: 1275–1283. 22 Bekris LM, Shephard C, Peterson M, et al. Glutathione-s-transferase M1 and T1 polymorphisms and associations with type 1 diabetes age-at-onset. Autoimmunity 2005; 38: 567–575. 23 Lee SG, Joo Y, Kim B, et al. Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans. Hum Genet 2005; 116: 319–328. 24 Cata~ no HC, Cueva JL, Cardenas AM, et al. Distribution of paraoxonase-1 gene polymorphisms and enzyme activity in a Peruvian population. Environ Mol Mutagen 2006; 47: 699–706.
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Omentin serum levels and omentin gene Val109Asp polymorphism in patients with psoriasis Hakan Turan1, Kursat Oguz Yaykasli2, Hatice Soguktas2, Emine Yaykasli2, Msc, Cihangir Aliagaoglu1, Teoman Erdem3, Mutlu Karkucak4, Ertugrul Kaya5, Taner Ucgun6, and Anzel Bahadir7
Departments of1 Dermatology, Duzce University Medical Faculty, 2Medical Genetics, Duzce University Medical Faculty, 3 Dermatology, Sakarya University Education and Research Hospital, 4 Medical Genetics, Sakarya University Education and Research Hospital, 5 Pharmacology, Duzce University Medical Faculty, 6Biochemistry, Duzce University Medical Faculty, and 7Biophysics, Duzce University Medical Faculty, Duzce, Turkey
Abstract Background Psoriasis is a chronic inflammatory disease of uncertain pathogenesis. Omentin is a new adipokine with anti-inflammatory properties; however, the relationship between psoriasis and omentin has not been fully established yet. Objectives This study was designed to evaluate the relationship between psoriasis and omentin serum levels and Val109Asp polymorphism in exon 4 of the omentin gene. Methods Forty-nine patients with plaque-type psoriasis and 39 healthy subjects were included in the study. Omentin concentrations were determined by using enzyme-linked immunosorbent assay. Val109Asp polymorphism in exon 4 of the omentin gene was assessed by the polymerase chain reaction–restriction fragment length polymorphism
Correspondence Dr. Hakan Turan, Assistant Professor Department of Dermatology Duzce University Medical Faculty Konuralp 81000 Duzce Turkey E-mail: [email protected] Conflict of interest: None declared. doi: 10.1111/ijd.12306
method. Genotypes were determined according to the bands formed in agarose electrophoresis gels. In the statistical analysis, the level of significance was set at P < 0.05. Results The serum omentin levels of the patients with psoriasis (354.2 152.0) were found to be significantly lower than those in the control group (488.7 190.3) (P = 0.001). A moderate level negative correlation was determined between serum omentin level and body mass index and waist circumference. No significant differences were observed between the patient and control groups in terms of the genotype and allele frequency of Val109Asp polymorphism in exon 4 of the omentin gene (P > 0.05). Conclusions Omentin serum levels were determined to be low in patients with psoriasis. No significant difference was found regarding Val109Asp polymorphism of the omentin gene. To the best of our knowledge, our study is the first clinical study to examine the relationship between psoriasis and omentin in terms of serum and genomic levels.
Introduction Psoriasis is a chronic, relapsing inflammatory disease with a heterogeneous genetic background that affects approximately 1–3% of the Caucasian population. The pathogenesis of psoriasis is still unknown. Adipose tissue is a metabolically active organ that releases various bioactive peptides known as adipokines, which contribute to the regulation of vital functions, such as insulin-mediated processes, lipid and glucose metabolism, vascular changes, and inflammation.1,2 Omentin, a new adipokine secreted by the stromal vascular cells of visceral adipose tissue,3 is considered associated with vascular, metabolic, and various chronic inflammatory diseases.4–7 There is currently only one study in the ª 2013 The International Society of Dermatology
literature that examines the relationship between psoriasis and serum omentin levels.8 The human omentin gene consists of eight exons and seven introns located on chromosome 1q21.39. To our knowledge, the literature includes only one study on omentin gene polymorphism. Sch€ affler et al.4 examined Val109Asp polymorphism in exon 4 of the omentin gene in type 2 diabetes and chronic inflammatory bowel disease. This polymorphism was investigated in relation to clinical parameters and in terms of the impact of pathogenesis; the effect of polymorphism on the omentin serum levels was not examined. The objective of this study was to compare the serum omentin levels of patients with psoriasis and control groups and to assess the role of Val109Asp polymorphism International Journal of Dermatology 2013
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2
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Omentin levels and polymorphism in psoriasis
of the omentin gene in the pathogenesis of psoriasis and its effect on omentin levels.
CTCTCCTTCTTCTCCAGCCCAT-3′.10 PCR primers for codon 109 were used to generate a 471 bp product containing the polymorphic sites. The PCR products were digested with the
Materials and Methods Study subjects A total of 49 patients with plaque-type psoriasis who presented to our outpatient clinic between May 2011 and July 2012, as well as 39 healthy controls, were included in the study. Approval for the study was obtained from the local ethics committee. All participants gave their written informed consent for participation in the medical research, and the investigations were conducted in accordance with the principles of the Declaration of Helsinki. The study exclusion criteria included the administration of any systemic treatment in the previous six months and topical treatment in the previous month, psoriatic arthritis, metabolic syndrome and metabolic risk, diabetes mellitus, polycystic ovary syndrome, hepatic and renal disease, malignancy, smoking, and the use of chronic medication. The age, sex, waist circumference, height, weight, and body mass index (BMI) of all the participants were recorded. In addition, disease duration and psoriasis area severity index (PASI) of the participants in the patient group were measured. Clinical and laboratory measurements Body mass index was calculated as kg/m2, and all participants were classified as normal weight (18–25), overweight (25–30), or obese (>30). Waist circumference was measured at the midpoint between the lower border of the rib cage and the iliac crest. Psoriasis was evaluated as mild (PASI 12). Metabolic syndrome was assessed according to the US National Cholesterol Education Program Adult Treatment Panel III guidelines.9 All blood samples were collected in the morning after a 12-hour overnight fast. Within 15 minutes after collection, the blood samples were centrifuged at 2.750 g for 10 minutes. The supernatant part was transferred to polypropylene tubes and stored at –80 °C until analysis. Serum omentin levels were assessed using a commercial enzyme-linked immunosorbent assay kit (Bio Vendor, Brno, Czech Republic). DNA extraction and genotyping of omentin (Val109Asp) Blood samples were obtained from the patient and control groups and collected in EDTA tubes. Genomic DNA was extracted from whole blood using a DNA isolation kit (PureLink; Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s instructions, and the samples were stored at –20 °C until analysis by the polymerase chain reaction (PCR)–restriction fragment length polymorphism method. The genotype at the omentin gene Val109Asp polymorphism was determined using the PCR–restriction fragment length polymorphism method by the following primers: forward 5′GAGCCTTTAGGCCATGTCTCT-3′ and reverse 5′International Journal of Dermatology 2013
restriction enzymes AccI (NEB, Hitchin, Herts, UK) at 37 °C for 16 hours and analyzed on a 3% agarose gel. Val/Val individuals had 274 bp and 197 bp fragments; Val/Asp individuals had 471 bp, 274 bp, and 197 bp fragments; and Asp/Asp individuals had only a 471 bp fragment.
Statistical analysis Statistical analyses were performed using PASW 18 statistical software (ver. 18.0 for Windows; SPSS Inc., Chicago, IL, USA). Normality analyses of continuous variables were performed with histogram curves. Continuous variables were presented as mean SD, and independent samples t tests and Mann– Whitney U tests were used when comparing the two groups. Spearman’s test was performed for determining linear correlations between serum omentin levels and waist circumference, BMI, disease duration, and PASI scores. Genotype and allele frequencies were compared by using a chisquared test, and the results were presented as frequency and percentage. P < 0.05 was considered statistically significant.
Results Clinical and demographic characteristics of the patient and control groups are summarized in Table 1. There were no differences between the two groups in terms of age, sex, BMI, or waist circumference. PASI scores were between 1 and 26, with an average of 5.02 5.38 (mean SD). According to PASI score severity, 42 patients were in the mild severity group, and seven patients were in the moderate and severe groups. Psoriasis disease duration was 1–40 years, with a mean value of 11.54 9.99 (mean SD). Serum omentin levels were found to be significantly lower (P = 0.001) in the patients with psoriasis (354.2 152.0) compared to the control group (488.7 190.3). The serum omentin levels of patients with mild and moderate–severe psoriasis were Table 1 Clinical and demographic characteristics of the patient group and control group
Parameters Gender, male/female Age (years SD) Waist circumferences (cm SD) BMI (kg/m2 SD) PASI Disease duration (year) Omentin, ng/mL
Patient group n = 49
Control group n = 39
P value
23/26 37.4 15.2 90.7 5.35
20/19 32.8 7.1 86.05 12.16
NS NS NS
25.02 3.2 N/A N/A 488.7 190.3
NS N/A N/A 0.001
26.5 5.02 11.54 354.2
5.7 5.38 9.99 152.0
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Turan et al.
Omentin levels and polymorphism in psoriasis
357.2 146.3 and 336.6 194.7, respectively, with no statistically significant difference (P > 0.05). A significant relationship and a moderate negative correlation were detected between serum omentin levels and BMI in the patient (P = 0.02, r = –0.447) and control (P = 0.04, r = –0.421) groups. In addition, there was a significant relationship and a moderate negative correlation between serum omentin levels and waist circumference in the patient (P = 0.013, r = – 0.463) and control (P = 0.018, r = – 0.417) groups. No significant relationship was found between serum omentin levels and disease duration or between serum omentin levels and PASI score. When omentin gene Val109Asp polymorphism was investigated, it was observed that 33 patients (67%) in the psoriasis group had Asp/Asp genotype, 14 (29%) had Asp/Val genotype, and two (4%) had Val/Val genotype. In the control group, 25 (64%) had Asp/Asp genotype, 11 (28%) had Asp/Val genotype, and three (8%) had Val/ Val genotype. Regarding genotype distribution, no statistical significance was determined between the patients with psoriasis and the control group (P > 0.05) (Table 2). Regarding omentin gene Val109Asp polymorphism, the frequency of the polymorphic Val allele was observed to be 18% in the patient group and 22% in the control group. No statistical significance was determined, although the Val allele was high in the patients with psoriasis group (Table 2). Discussion In this study, serum omentin levels and Val109Asp polymorphism in the omentin gene were investigated in patients with psoriasis. Serum omentin levels were lower in the patients with psoriasis compared to the control group. However, there were no significant differences between the patient and control groups in terms of the genotype and allele frequency of Val109Asp polymorphism in the omentin gene. To our knowledge, our study is the first clinical study in the literature to examine the relationship between psoriasis and omentin in terms of serum and genomic levels. Table 2 The distribution of genotypes in the patient group and control group Variables
Patient group n = 49
Genotypes Asp/Asp 33 (67%) Asp/Val 14 (29%) Val/Val 2 (4%) Frequency of alleles Asp 82% Val 18%
Control group n = 39
P value
25 (64%) 11 (28%) 3 (8%)
0.926 0.841 0.651
78% 22%
0.595
ª 2013 The International Society of Dermatology
Medical genetics
As the immunological basis of psoriasis has been understood better in recent years, it has been noted with greater emphasis that psoriasis is not limited to the skin but that it is a systemic disease with various comorbidities. Patients with psoriasis carry a high risk of comorbidities such as vascular diseases and metabolic syndrome.11 Chronic inflammation is known to be the main pathological process that causes skin involvement and comorbidities in psoriasis. Adipokines secreted by the adipose tissue are proteins that regulate nutrient metabolism, immune response, and inflammation.12 Omentin is an adipokine first discovered in 2003 and identified from visceral omental fat tissue.13 It has been reported that serum omentin levels significantly decrease in obesity, polycystic ovary syndrome, atherosclerosis, and diabetes, and that it is negatively correlated with risk factors such as high body mass index, waist circumference, and insulin resistance.8,14,15 Omentin also has an anti-inflammatory effect that works through the nuclear factor (NF) jb route16. NF-jB is a potent proinflammatory transcription factor responsible for the onset and amplification of the inflammatory response.17 Activation and DNA binding of NF-jB because of the degradation of inhibitory proteins (IkBa) induce the transcription of target genes responsible for immune response and inflammatory functions.18 In recent years, there has been evidence that NF-jB plays a role in the pathogenesis of psoriasis and other inflammatory diseases.19–21 Zhong et al.16 have shown that omentin inhibits tumor necrosis factor a-induced IkBa degradation and NF-jB activity in human umbilical vein endothelial cells. This information suggests that omentin may be closely associated with psoriasis pathogenesis via NF-jB inhibition. The biological effects of omentin on psoriasis and the effects of serum levels and psoriasis on omentin levels have not yet been fully understood. There is currently a single study on the relationship between psoriasis and omentin. Ismail and Mohamed8 investigated the relationship of serum omentin levels with disease duration and severity and obesity markers in patients with psoriasis and concluded that serum omentin levels were significantly lower in the psoriasis group compared to the control group (with no difference in waist circumference and BMI). In their study, exclusion criteria included the factors that affected omentin serum levels. Consequently, BMI and waist circumference and serum omentin levels were negatively correlated. No relationship was found between the duration and severity of disease and omentin serum levels. It was suggested that the low serum omentin levels could have contributed to the increased prevalence of cardiovascular diseases in patients with psoriasis. However, considering the exclusion criteria of the study and International Journal of Dermatology 2013
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the absence of any difference between obesity markers of the two groups, no comment was made on why omentin serum levels were lower in patients with psoriasis. In our study, similar to the results obtained by Ismail and Mohamed,8 omentin levels were found to be lower in patients with psoriasis once the parameters that could affect the omentin serum levels were excluded. This result has led us to consider that low omentin levels might contribute to the pathogenesis of both psoriasis and accompanying cardiovascular and metabolic diseases by triggering inflammation. We determined a negative correlation at moderate level between serum omentin levels and BMI and waist circumference in both the patient and control groups. We were unable to find any relationship between omentin serum levels and disease duration or PASI score. Although a numeric difference was observed between the serum omentin levels of mild (357.2 146.3) and moderate–severe (336.6 194.7) patients, there was no statistical difference. This result may be explained by the low number of patients in the moderate–severe group. There are studies in literature that suggest that gene polymorphism might affect the production, activity, and level of the product.22–24 As such, we considered that a possible polymorphism in the omentin gene might affect serum omentin levels. Sch€affler et al.10 investigated the relationships between Val109Asp polymorphism of omentin gene and type 2 diabetes mellitus, ulcerative colitis, and Crohn’s disease, in which omentin may have a pathogenic role; however, they found no significant relationship between the diseases and the genotype. In this study, we also evaluated the effects of omentin Val109Asp polymorphism on omentin serum levels and disease pathogenesis. Despite the high rate of Val allele frequency in the patient group, no statistical differences were detected between the groups in terms of genotype and allele frequency. We are of the opinion that the low omentin levels in the patient group might not be associated with Val109Asp polymorphism but may have resulted from another polymorphism in the gene or other factors that have not been determined yet. Similar to the previous study, omentin serum levels were found to be lower in the patient group compared to the control group. When the omentin gene was examined with regard to Val109Asp polymorphism, no difference was determined between the patient and control groups; thus, it was concluded that this polymorphism had no effect on omentin serum levels. In our study, although the sample size is not too small overall, it might be inadequate for the subcategories. Therefore, the results obtained in this study should be supported by other studies conducted with larger patient groups and by assessing other gene polymorphisms. International Journal of Dermatology 2013
Acknowledgments This study was supported by the Duzce University Scientific Research Projects Commission (project no. 2011.04.03.082). References 1 Guerre-Millo M. Adipose tissue and adipokines: for better or worse. Diabetes Metab 2004; 30: 13–19. 2 Ronti T, Lupattelli G, Mannarino E. The endocrine function of adipose tissue: an update. Clin Endocrinol (Oxf) 2006; 64: 355–365. 3 Wang Y, Lam KS, Kraegen EW, et al. Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin Chem 2007; 53: 34–41. 4 Sch€ affler A, Zeitoun M, Wobser H. Frequency and significance of the novel single nucleotide missense polymorphism Val109Asp in the human gene encoding omentin in Caucasian patients with type 2 diabetes mellitus or chronic inflammatory bowel diseases. Cardiovasc Diabetol 2007; 6: 3. 5 Senolt L, Polansk a M, Filkov a M, et al. Vaspin and omentin: new adipokines differentially regulated at the site of inflammation in rheumatoid arthritis. Ann Rheum Dis 2010; 69: 1410–1411. 6 Shibata R, Ouchi N, Kikuchi R, et al. Circulating omentin is associated with coronary artery disease in men. Atherosclerosis 2011; 219: 811–814. 7 Pan HY, Guo L, Li Q. Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes. Diabetes Res Clin Pract 2010; 88: 29–33. 8 Ismail SA, Mohamed SA. Serum levels of visfatin and omentin-1 in patients with psoriasis and their relation to disease severity. Br J Dermatol 2012; 167: 436–439. 9 National Cholesterol Education Program (NCEP); Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation 2002; 106: 3143–3421. 10 Sch€ affler A, Neumeier M, Herfarth H, et al. Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue. Biochim Biophys Acta 2005; 1732: 96–102. 11 Gerdes S, Mrowietz U. Impact of comorbidities on the management of psoriasis. Curr Probl Dermatol 2009; 38: 21–36. 12 Hida K, Wada J, Zhang H, et al. Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats. J Lipid Res 2000; 41: 1615–1622. ª 2013 The International Society of Dermatology
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13 Yang R, Xu A, Pray J, et al. Cloning of omentin a new adipocytokine from omental fat tissue in humans. Diabetes 2003; (Suppl 1): A1. 14 de Souza Batista CM, Yang RZ, Lee MJ, et al. Omentin plasma levels and gene expression are decreased in obesity. Diabetes 2007; 56: 1655–1661. 15 Tan BK, Adya R, Farhatullah S, et al. Omentin-1, a novel adipokine, is decreased in overweight insulin-resistant women with polycystic ovary syndrome: ex vivo and in vivo regulation of omentin-1 by insulin and glucose. Diabetes 2008; 57: 801–808. 16 Zhong X, Li X, Liu F, et al. Omentin inhibits TNF-a-induced expression of adhesion molecules in endothelial cells via ERK/NF-jB pathway. Biochem Biophys Res Commun 2012; 425: 401–406. 17 Kwak JH, Jung JK, Lee H. Nuclear factor-kappa B inhibitors; a patent review (2006–2010). Expert Opin Ther Pat 2011; 21: 1897–1910. 18 Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 1999; 18: 6853–6866. 19 Doger FK, Dikicioglu E, Ergin F, et al. Nature of cell kinetics in psoriatic epidermis. J Cutan Pathol 2007; 34: 257–263.
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20 Marchetti S, Gamas P, Belhacene N, et al. The caspase-cleaved form of LYN mediates a psoriasis-like inflammatory syndrome in mice. EMBO J 2009; 28: 2449–2460. 21 Lizzul PF, Aphale A, Malaviya R. Differential expression of phosphorylated NF-kappaB/RelA in normal and psoriatic epidermis and downregulation of NF-kappaB in response to treatment with etanercept. J Invest Dermatol 2005; 124: 1275–1283. 22 Bekris LM, Shephard C, Peterson M, et al. Glutathione-s-transferase M1 and T1 polymorphisms and associations with type 1 diabetes age-at-onset. Autoimmunity 2005; 38: 567–575. 23 Lee SG, Joo Y, Kim B, et al. Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans. Hum Genet 2005; 116: 319–328. 24 Cata~ no HC, Cueva JL, Cardenas AM, et al. Distribution of paraoxonase-1 gene polymorphisms and enzyme activity in a Peruvian population. Environ Mol Mutagen 2006; 47: 699–706.
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