LETTERS TO THE EDITOR
Polymorphism in DPPIV Gene in Acute Pancreatitis To the Editor: ssues surrounding acute pancreatitis (AP), which is still increasing and insufficiently examined, encouraged our search for new analytical methods. Here, we bring new insight into the role of single nucleotide polymorphisms in pancreatitis development, and this study forms an introduction to individualized research on the impact of environmental factors, including food, in pancreatic secretory disorders. Although gallstones and alcohol abuse are the main risk factors for AP, it may also arise as a consequence of glucose metabolic disorder treatment.1,2 DPPIV is a serine protease that preferentially cleaves Xaa-Pro and Xaa-Ala dipeptides from the N-termini of polypeptides,3 and the breakdown of these exogenous peptides presumably results in inactivating their opioid activity.4 DPPIV has also a significant role in glucose metabolism. This is based on its enzymatic mechanism degrading both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which affect postprandial insulin secretion and inhibit glucagon secretion. Glucagon-like peptide-1 beneficially influences islet of Langerhans β cells by inhibiting apoptosis5; therefore, DPPIV
I
degradation of GLP-1 and GIP can induce glucose metabolism disorders. According to clinical studies, DPPIV inhibitors improve glucose tolerance,6 because their administration to AP patients prevents GLP-1 degradation, prolongs its half-life, and exerts beneficial effects on pancreatic endocrine function.7 Both GIP and GLP-1 concentrations increase rapidly postprandially but are quickly reduced by DPPIV activity. Abnormalities in this process therefore lead to glucose metabolism disorders.5,8 Moreover, Dobrian et al8 determined in their studies on local inflammation in obese mice adipose tissue and pancreatic islets that the DPPIV inhibitor sitagliptin significantly reduced messenger RNA expression of inflammatory cytokines, including IL-12 and IL-6. They further established that this DPPIV inhibitor exerted its anti-inflammatory effects with coexisting insulinotropic activity. This explains why therapies based on GIP/ GLP-1 receptor agonists and DPPIV inhibitors are beneficial in treating diseases related to pancreatic dysfunction. Our study compares the frequency of DPPIV (A/G) gene rs7608798 in healthy controls (112 individuals, 22 females and 90 males; mean age ranging from 23 to 58 years; all patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for alcohol dependence) and in 186 patients diagnosed with
TABLE 1. Genotype and Allele Frequencies of rs7608798 in DPPIV Gene Polymorphism in Studied Groups and G-allele AP Association Genotypes, N (%) Research Group
AA
AG
AP population M + F (n = 186) Control group M + F (n = 112) Studied male (AP + C) (n = 198) AP male (n = 108) Control male (n = 90) Studied female (AP + C) (n = 100) AP female (n = 78) Control female (n = 22)
GG
22 (30.1) 108 (58.1) 56 (11.8) 1 (0.9) 38 (33.9) 73 (65.2) 11 (5.6) 95 (48.0) 92 (46.5) 10 (9.3) 66 (61.1) 32 (29.6) 1 (1.1) 29 (32.2) 60 (66.7) 12 (12.0) 51 (51.0) 37 (37.0) 12 (15.4) 42 (53.8) 24 (30.8) 0 (0.0) 9 (41.0) 13 (59.0) OR (95% CI) AG + AA vs GG AP vs control 4.95 (3.23–7.58) Female (AP + C) vs male (AP + C) 1.59 (1.07–2.37) AP male vs control male 5.2 (3.12–6.70) AP female vs control female 5.78 (2.50–7.12) Control male vs control female 1.34 (0.57–3.15) AP male vs AP female 1.02 (0.63–1.68)
Frequency of Alleles A
G
0.41 0.18 0.30 0.40 0.17 0.38 0.58 0.20
0.59 0.82 0.70 0.60 0.83 0.62 0.42 0.80 P
Polymorphism in DPPIV Gene in Acute Pancreatitis To the Editor: ssues surrounding acute pancreatitis (AP), which is still increasing and insufficiently examined, encouraged our search for new analytical methods. Here, we bring new insight into the role of single nucleotide polymorphisms in pancreatitis development, and this study forms an introduction to individualized research on the impact of environmental factors, including food, in pancreatic secretory disorders. Although gallstones and alcohol abuse are the main risk factors for AP, it may also arise as a consequence of glucose metabolic disorder treatment.1,2 DPPIV is a serine protease that preferentially cleaves Xaa-Pro and Xaa-Ala dipeptides from the N-termini of polypeptides,3 and the breakdown of these exogenous peptides presumably results in inactivating their opioid activity.4 DPPIV has also a significant role in glucose metabolism. This is based on its enzymatic mechanism degrading both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which affect postprandial insulin secretion and inhibit glucagon secretion. Glucagon-like peptide-1 beneficially influences islet of Langerhans β cells by inhibiting apoptosis5; therefore, DPPIV
I
degradation of GLP-1 and GIP can induce glucose metabolism disorders. According to clinical studies, DPPIV inhibitors improve glucose tolerance,6 because their administration to AP patients prevents GLP-1 degradation, prolongs its half-life, and exerts beneficial effects on pancreatic endocrine function.7 Both GIP and GLP-1 concentrations increase rapidly postprandially but are quickly reduced by DPPIV activity. Abnormalities in this process therefore lead to glucose metabolism disorders.5,8 Moreover, Dobrian et al8 determined in their studies on local inflammation in obese mice adipose tissue and pancreatic islets that the DPPIV inhibitor sitagliptin significantly reduced messenger RNA expression of inflammatory cytokines, including IL-12 and IL-6. They further established that this DPPIV inhibitor exerted its anti-inflammatory effects with coexisting insulinotropic activity. This explains why therapies based on GIP/ GLP-1 receptor agonists and DPPIV inhibitors are beneficial in treating diseases related to pancreatic dysfunction. Our study compares the frequency of DPPIV (A/G) gene rs7608798 in healthy controls (112 individuals, 22 females and 90 males; mean age ranging from 23 to 58 years; all patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for alcohol dependence) and in 186 patients diagnosed with
TABLE 1. Genotype and Allele Frequencies of rs7608798 in DPPIV Gene Polymorphism in Studied Groups and G-allele AP Association Genotypes, N (%) Research Group
AA
AG
AP population M + F (n = 186) Control group M + F (n = 112) Studied male (AP + C) (n = 198) AP male (n = 108) Control male (n = 90) Studied female (AP + C) (n = 100) AP female (n = 78) Control female (n = 22)
GG
22 (30.1) 108 (58.1) 56 (11.8) 1 (0.9) 38 (33.9) 73 (65.2) 11 (5.6) 95 (48.0) 92 (46.5) 10 (9.3) 66 (61.1) 32 (29.6) 1 (1.1) 29 (32.2) 60 (66.7) 12 (12.0) 51 (51.0) 37 (37.0) 12 (15.4) 42 (53.8) 24 (30.8) 0 (0.0) 9 (41.0) 13 (59.0) OR (95% CI) AG + AA vs GG AP vs control 4.95 (3.23–7.58) Female (AP + C) vs male (AP + C) 1.59 (1.07–2.37) AP male vs control male 5.2 (3.12–6.70) AP female vs control female 5.78 (2.50–7.12) Control male vs control female 1.34 (0.57–3.15) AP male vs AP female 1.02 (0.63–1.68)
Frequency of Alleles A
G
0.41 0.18 0.30 0.40 0.17 0.38 0.58 0.20
0.59 0.82 0.70 0.60 0.83 0.62 0.42 0.80 P
