International Journal of Neuroscience, 2014; 124(9): 642–651 Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 0020-7454 print / 1543-5245 online DOI: 10.3109/00207454.2013.873978
META-ANALYSIS
Association between endothelial nitric oxide synthase gene polymorphism (T-786C) and ischemic stroke susceptibility: a meta-analysis Ruozhuo Liu,1,∗ Peiliang Geng,2,∗ Minghui Ma,3,∗ Shengyuan Yu,1 Xiaolin Wang,1 Wei Zhang,1 and Hai Di1 Int J Neurosci Downloaded from informahealthcare.com by Dicle Univ. on 11/16/14 For personal use only.
1
Department of Neurology, Chinese PLA General Hospital, Beijing, China; 2 Key Laboratory of Oncology, Cancer Center, Division of Internal Medicine, Chinese PLA General Hospital and Chinese PLA Medical School, Beijing, China; 3 Ministry of Resource Construction, Medical Library of the Chinese PLA, Academy of Military Medical Sciences, Beijing, China Background: The endothelial nitric oxide synthase (eNOS) T-786C polymorphism has been implicated in a number of studies investigating ischemic stroke (IS), yet previously published studies showed inconsistent results that recent meta-analyses have not resolved. Methods: In the comprehensive meta-analysis of 12 association studies involving 2836 IS cases and 3354 control subjects, we used a more stringent inclusion method and summarized data on the association of eNOS T-786C polymorphism and IS susceptibility. Results: We found a significantly lowered IS risk under the CC vs. TT genetic model (odds ratio, OR = 0.53, 95% confidence interval, CI = 0.29–0.98, p = 0.160, I2 = 45.5%) by random effects model in Caucasians and under the allele model C vs. T (OR = 0.42, 95% CI = 0.21–0.87) by fixed effects model in African-Americans. In addition, a significant increased risk of IS was observed in Asians (C vs. T: OR = 1.14, 95% CI = 1.02–1.28, p = 0.990, I2 = 0.0%) by fixed effects model. Stratified analysis by mean age also showed that the allele C carriers, compared with the allele T allele carriers, had higher risk of suffering IS (OR = 1.16, 95% CI = 1.03–1.31) in the population of 60–65 years without heterogeneity. Conclusions: The combined results suggest that eNOS T-786C polymorphism may be associated with IS susceptibility among the population between 60 and 65 years in particular. KEYWORDS: endothelial nitric oxide synthase, T-786C polymorphism, ischemic stroke, meta-analysis
Introduction Stroke is the second most common cause of death and major cause of disability throughout the world [1]. There are 2.5 million newly diagnosed stroke cases with approximately 1.6 million deaths each year in China [2]. The huge burden will increase greatly during the next 20 years [1]. Stroke mainly originates from ischemic stroke (IS) known to be a multifactorial disorder. In addition to atherosclerosis, heart disease, vasculitis, hypertension, smoking, genetic susceptibility factors may be also involved in IS due to endothelial dysfunction [3, 4]. The endothelial nitric oxide synthase (eNOS) is a critical enzyme synthesizing nitric oxide (NO) from LReceived 21 August 2013; revised XX 20XX; accepted 8 December 2013. ∗
First authors: Ruozhuo Liu, Peiliang Geng, and Minghui Ma. Correspondence: Shengyuan Yu, Department of Neurology, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing 100853, China. Tel: +86-10-55499118. Fax: +86-10-88626299. E-mail: [email protected]
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arginine [5]. NO plays a physiological role in several biological processes including the regulation of cerebral blood flow, thermogenesis, and the modulation of neuronal activity [6]. Most NO actions are mediated by cyclic guanosine monophosphate pathway [7]. The abnormality of endothelial NO synthesis leads to impaired cerebral auto-regulation and endothelial dysfunction, which is related to atherosclerosis, IS, and various other vessel diseases [8–11]. The eNOS gene is mapped to chromosome 7q35–36 and consists of 26 exons spaning 21 kb [12–14]. Several polymorphisms such as G894T in exon 7 and 4b/a in intron 4 have been widely investigated in terms of the association with IS predisposition [15–17]. Another representative eNOS gene polymorphism, T-786C (rs2070744) located in the promoter region, was reported to alter eNOS gene expression and reduce the eNOS gene promoter activity [18]. T-786C polymorphism has been additionally demonstrated to be correlated with IS. However, various studies designed to
eNOS T-786C polymorphism and ischemic stroke
investigate the association between this polymorphism and IS showed contradictory results [19–22]. Therefore, to better evaluate the association between T-786C polymorphism and IS and to define the disease risk associated with the studied polymorphism, we performed a meta-analysis of present and previous available data that evaluated allelic and genotypic frequencies of T-786C polymorphism in IS.
Materials and methods
Int J Neurosci Downloaded from informahealthcare.com by Dicle Univ. on 11/16/14 For personal use only.
Data sources Electronic databases including PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Chinese WanFang were searched until April 2013 for all case-control studies evaluating the association between T-786C polymorphism and IS. The following key words were used in our search strategy: (endothelial nitric oxide synthase) or (eNOS) and (T-786C) or (rs2070744) and (polymorphism) or (polymorphisms) and (ischemic stroke). We considered full articles without language restrictions. In addition, we manually searched the refer-
ence lists of all primary articles, meta-analyses and review articles.
Study eligibility We defined the following criteria for inclusion: (1) the study had a case-control design published as a full paper; (2) assessing the association of T-786C polymorphism and IS; (3) supplied information on genotype frequencies to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs).
Data extraction Two reviewers independently extracted data from the retrieved studies and entered them into a customized database. Consensus on all items was reached by discussion and consultation with a senior reviewer. The extracted data included first author, year of publication, country of origin, ethnicity, gender, mean age, study size, and genotype frequencies. For studies with overlapping cases and/or controls, the most recent or the largest study was considered.
Figure 1. The flow chart of the included studies in the meta-analysis.
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2014 Informa Healthcare USA, Inc.
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Int J Neurosci Downloaded from informahealthcare.com by Dicle Univ. on 11/16/14 For personal use only.
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R. Liu et al.
Figure 2. Forest plot of IS risk associated with the eNOS T-786C polymorphism stratified by ethnicity. CC vs. TT model by the random
effects for each of the 12 published studies. For each study, the estimates of OR and its 95% CI were plotted with a box and a horizontal line. The symbol filled diamond indicates pooled OR and its 95% CI. A significant association of the eNOS T-786C polymorphism with IS risk was found in Caucasians.
Statistical analysis Hardy–Weinberg equilibrium (HWE) of genotype distribution in the controls of eligible studies was checked by Pearson’s χ 2 test (p < 0.10 means deviation from HWE). The strength of association between T-786C polymorphism and IS risk was evaluated by crude ORs with corresponding 95% CIs under the following genetic models: the homozygote model (CC vs. TT), the dominant model (CC + CT vs. TT), the recessive model (CC vs. CT + TT), the allele model (C vs. T), and the heterozygote model (CT vs. TT). The significance of OR was determined by Z-test with p value < 0.10 as statistical significance. Between-study heterogeneity was tested by the Q-test and I2 statistics [23]. p < 0.10 or I2 >50% indicated
presence of heterogeneity across studies. The OR estimates were pooled by a fixed effects model (MantelHaenszel method) [24] in the absence of significant heterogeneity; otherwise, the random effects model (DerSimonian-Laird method) [25] was selected. Subgroup analysis based on ethnicity (Caucasian, AfricanAmerican, or Asian) and mean age (65) were also performed to detect the heterogeneity sources. Sensitivity analysis was performed by excluding each study to examine the stability and reliability of the results. Publication bias was determined by Begg’s funnel plot and Egger’s test [26], with a significant level fixed at p < 0.10. All data were analyzed using Stata software (version 12.0, Stata Corp LP, College Station, TX). International Journal of Neuroscience
Int J Neurosci Downloaded from informahealthcare.com by Dicle Univ. on 11/16/14 For personal use only.
eNOS T-786C polymorphism and ischemic stroke
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Figure 3. Forest plot of IS risk associated with the eNOS T-786C polymorphism stratified by ethnicity. CC + TC vs. TT model by the fixed effects for each of the 12 published studies. For each study, the estimates of OR and its 95% CI were plotted with a box and a horizontal line. The symbol filled diamond indicates pooled OR and its 95% CI. No significant association of the eNOS T-786C polymorphism with IS risk was found.
Results Study characteristics We identified a total of 87 relevant publications that matched our search terms at initial screening. After excluding the studies that did not satisfy the inclusion criteria, 12 publications [19–22, 27–34] were included in the present meta-analysis (Figure 1). The data collected from the eligible studies are summarized in Table 1. Since the study by Howard et al. [20] included two independent study groups with different ethnicities, which were treated separately and divided into Caucasian and African-American. Therefore, the meta-analysis finally included 13 studies with 2836 IS cases and 3354 con C
2014 Informa Healthcare USA, Inc.
trol subjects. The ethnicity of eligible subjects involved populations ranging from African-American (n = 1), Caucasian (n = 3) and Asian (n = 9). Only one [29] of the 13 studies was slightly deviated from HWE.
Quantitative synthesis The main results of meta-analysis and heterogeneity were listed in Table 2. Two of the five models suggested remarkable between-study heterogeneity, thus both fixed effects model and random effects model were performed to calculate the pooled estimates. Overall, no significant association between T-786C polymorphism and IS was observed under all genetic models (Figures 2–4).
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UK USA USA China Singapore Turkey India Bahraini Korea Korea China China China
Hassan (2004) Howarda (2005) Howardb (2005) Cheng (2008) Moe (2008) Yemici (2009) Majumdar (2010) Saidi (2010) Kim (2010) Song (2010) Yan (2011) Li (2011) Meng (2012)
Caucasian African-American Caucasian Asian Asian Caucasian Asian Asian Asian Asian Asian Asian Asian
Ethnicity F/M F F F/M F/M F/M F/M F/M F/M F/M F/M F/M F/M
Gender
Study size 298 50 50 309 120 67 129 329 223 265 558 300 138
Mean age 67.10 ± 10.26 39 39 61.34 ± 10.26 62.5 ± 1.1 63.5 ± 10.5 29.71 ± 10.82 61.8 ± 12.2 61.84 62.22 ± 11.90 61.0 ± 9.8 61.57 ± 5.82 67.6 ± 10.9 115 39 20 240 86 25 70 162 186 218 434 230 124
TT
, :different ethnicities in one study; F/M: female/male; Hardy-Weinberg equilibrium (HWE).
a b
Country 143 11 20 58 27 33 50 131 37 43 122 66 14
TC
Case
40 0 10 11 7 9 9 36 0 4 2 4 0
CC 373 89 60 538 199 83 190 455 409 479 990 526 262
T 223 11 40 80 41 51 68 203 37 51 126 74 14
C
599 75 117 309 207 79 129 444 206 232 557 300 100
Study size
220 42 40 250 152 35 69 249 171 193 451 238 90
TT
Characteristics of studies included in the meta-analysis for an association between the eNOS T-786C polymorphism and IS risk.
First author (year)
Table 1.
Int J Neurosci Downloaded from informahealthcare.com by Dicle Univ. on 11/16/14 For personal use only.
283 27 59 56 52 41 55 162 35 39 96 57 10
TC
96 6 18 3 3 3 5 33 0 0 10 5 0
CC
Control
723 111 139 556 356 111 193 660 377 425 998 533 190
T
475 39 95 62 58 47 65 228 35 39 116 67 10
C
Y Y Y Y Y N Y Y Y Y Y Y Y
HWE
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Ph
0.97 (0.78, 1.21) 0.85 (0.63, 1.16) 1.13 (0.99, 1.28) 1.05 (0.95, 1.17)
0.921 0.314 0.999 0.912
0.98 (0.81, 1.19) 0.846 0.50 (0.23, 1.08) NA 1.11 (0.98, 1.26) 0.998
OR (95% CI)
CC + TC vs. TT
0.0% 13.6% 0.0% 0.0%
0.0% NA 0.0%
I
2
Ph
0.84 (0.56, 1.24) NA 1.18 (0.46, 3.00) 0.203 1.71 (0.82, 3.54) 0.028 1.36 (0.85, 2.18) 0.013
1.25 (0.63, 2.49) 0.104 0.12 (0.01, 2.09) NA 1.55 (0.79, 3.03) 0.046
OR (95% CI)
CC vs. TC + TT I
2
NA 37.3% 57.6% 55.7%
55.9% NA 53.1%
Ph : pvalue of heterogeneity test; NA: not available; CI: confidence interval; OR, odds ratio; NA: not available.
NA 30.1% 54.0% 62.5%
0.39 (0.26, 0.58) NA 0.57 (0.24, 1.37) 0.239 1.13 (0.56, 2.27) 0.042 0.79 (0.47, 1.32) 0.003
I 45.4% NA 52.5%
Ph
2
0.53 (0.29, 0.98) 0.160 0.07 (0.00, 1.35) NA 1.05 (0.54, 2.05) 0.049
OR (95% CI)
CC vs. TT
Meta-analysis of the associations between the eNOS T-786C polymorphism and IS risk.
Ethnicity Caucasian African-American Asian Mean age >65
META-ANALYSIS
Association between endothelial nitric oxide synthase gene polymorphism (T-786C) and ischemic stroke susceptibility: a meta-analysis Ruozhuo Liu,1,∗ Peiliang Geng,2,∗ Minghui Ma,3,∗ Shengyuan Yu,1 Xiaolin Wang,1 Wei Zhang,1 and Hai Di1 Int J Neurosci Downloaded from informahealthcare.com by Dicle Univ. on 11/16/14 For personal use only.
1
Department of Neurology, Chinese PLA General Hospital, Beijing, China; 2 Key Laboratory of Oncology, Cancer Center, Division of Internal Medicine, Chinese PLA General Hospital and Chinese PLA Medical School, Beijing, China; 3 Ministry of Resource Construction, Medical Library of the Chinese PLA, Academy of Military Medical Sciences, Beijing, China Background: The endothelial nitric oxide synthase (eNOS) T-786C polymorphism has been implicated in a number of studies investigating ischemic stroke (IS), yet previously published studies showed inconsistent results that recent meta-analyses have not resolved. Methods: In the comprehensive meta-analysis of 12 association studies involving 2836 IS cases and 3354 control subjects, we used a more stringent inclusion method and summarized data on the association of eNOS T-786C polymorphism and IS susceptibility. Results: We found a significantly lowered IS risk under the CC vs. TT genetic model (odds ratio, OR = 0.53, 95% confidence interval, CI = 0.29–0.98, p = 0.160, I2 = 45.5%) by random effects model in Caucasians and under the allele model C vs. T (OR = 0.42, 95% CI = 0.21–0.87) by fixed effects model in African-Americans. In addition, a significant increased risk of IS was observed in Asians (C vs. T: OR = 1.14, 95% CI = 1.02–1.28, p = 0.990, I2 = 0.0%) by fixed effects model. Stratified analysis by mean age also showed that the allele C carriers, compared with the allele T allele carriers, had higher risk of suffering IS (OR = 1.16, 95% CI = 1.03–1.31) in the population of 60–65 years without heterogeneity. Conclusions: The combined results suggest that eNOS T-786C polymorphism may be associated with IS susceptibility among the population between 60 and 65 years in particular. KEYWORDS: endothelial nitric oxide synthase, T-786C polymorphism, ischemic stroke, meta-analysis
Introduction Stroke is the second most common cause of death and major cause of disability throughout the world [1]. There are 2.5 million newly diagnosed stroke cases with approximately 1.6 million deaths each year in China [2]. The huge burden will increase greatly during the next 20 years [1]. Stroke mainly originates from ischemic stroke (IS) known to be a multifactorial disorder. In addition to atherosclerosis, heart disease, vasculitis, hypertension, smoking, genetic susceptibility factors may be also involved in IS due to endothelial dysfunction [3, 4]. The endothelial nitric oxide synthase (eNOS) is a critical enzyme synthesizing nitric oxide (NO) from LReceived 21 August 2013; revised XX 20XX; accepted 8 December 2013. ∗
First authors: Ruozhuo Liu, Peiliang Geng, and Minghui Ma. Correspondence: Shengyuan Yu, Department of Neurology, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing 100853, China. Tel: +86-10-55499118. Fax: +86-10-88626299. E-mail: [email protected]
642
arginine [5]. NO plays a physiological role in several biological processes including the regulation of cerebral blood flow, thermogenesis, and the modulation of neuronal activity [6]. Most NO actions are mediated by cyclic guanosine monophosphate pathway [7]. The abnormality of endothelial NO synthesis leads to impaired cerebral auto-regulation and endothelial dysfunction, which is related to atherosclerosis, IS, and various other vessel diseases [8–11]. The eNOS gene is mapped to chromosome 7q35–36 and consists of 26 exons spaning 21 kb [12–14]. Several polymorphisms such as G894T in exon 7 and 4b/a in intron 4 have been widely investigated in terms of the association with IS predisposition [15–17]. Another representative eNOS gene polymorphism, T-786C (rs2070744) located in the promoter region, was reported to alter eNOS gene expression and reduce the eNOS gene promoter activity [18]. T-786C polymorphism has been additionally demonstrated to be correlated with IS. However, various studies designed to
eNOS T-786C polymorphism and ischemic stroke
investigate the association between this polymorphism and IS showed contradictory results [19–22]. Therefore, to better evaluate the association between T-786C polymorphism and IS and to define the disease risk associated with the studied polymorphism, we performed a meta-analysis of present and previous available data that evaluated allelic and genotypic frequencies of T-786C polymorphism in IS.
Materials and methods
Int J Neurosci Downloaded from informahealthcare.com by Dicle Univ. on 11/16/14 For personal use only.
Data sources Electronic databases including PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Chinese WanFang were searched until April 2013 for all case-control studies evaluating the association between T-786C polymorphism and IS. The following key words were used in our search strategy: (endothelial nitric oxide synthase) or (eNOS) and (T-786C) or (rs2070744) and (polymorphism) or (polymorphisms) and (ischemic stroke). We considered full articles without language restrictions. In addition, we manually searched the refer-
ence lists of all primary articles, meta-analyses and review articles.
Study eligibility We defined the following criteria for inclusion: (1) the study had a case-control design published as a full paper; (2) assessing the association of T-786C polymorphism and IS; (3) supplied information on genotype frequencies to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs).
Data extraction Two reviewers independently extracted data from the retrieved studies and entered them into a customized database. Consensus on all items was reached by discussion and consultation with a senior reviewer. The extracted data included first author, year of publication, country of origin, ethnicity, gender, mean age, study size, and genotype frequencies. For studies with overlapping cases and/or controls, the most recent or the largest study was considered.
Figure 1. The flow chart of the included studies in the meta-analysis.
C
2014 Informa Healthcare USA, Inc.
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Int J Neurosci Downloaded from informahealthcare.com by Dicle Univ. on 11/16/14 For personal use only.
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R. Liu et al.
Figure 2. Forest plot of IS risk associated with the eNOS T-786C polymorphism stratified by ethnicity. CC vs. TT model by the random
effects for each of the 12 published studies. For each study, the estimates of OR and its 95% CI were plotted with a box and a horizontal line. The symbol filled diamond indicates pooled OR and its 95% CI. A significant association of the eNOS T-786C polymorphism with IS risk was found in Caucasians.
Statistical analysis Hardy–Weinberg equilibrium (HWE) of genotype distribution in the controls of eligible studies was checked by Pearson’s χ 2 test (p < 0.10 means deviation from HWE). The strength of association between T-786C polymorphism and IS risk was evaluated by crude ORs with corresponding 95% CIs under the following genetic models: the homozygote model (CC vs. TT), the dominant model (CC + CT vs. TT), the recessive model (CC vs. CT + TT), the allele model (C vs. T), and the heterozygote model (CT vs. TT). The significance of OR was determined by Z-test with p value < 0.10 as statistical significance. Between-study heterogeneity was tested by the Q-test and I2 statistics [23]. p < 0.10 or I2 >50% indicated
presence of heterogeneity across studies. The OR estimates were pooled by a fixed effects model (MantelHaenszel method) [24] in the absence of significant heterogeneity; otherwise, the random effects model (DerSimonian-Laird method) [25] was selected. Subgroup analysis based on ethnicity (Caucasian, AfricanAmerican, or Asian) and mean age (65) were also performed to detect the heterogeneity sources. Sensitivity analysis was performed by excluding each study to examine the stability and reliability of the results. Publication bias was determined by Begg’s funnel plot and Egger’s test [26], with a significant level fixed at p < 0.10. All data were analyzed using Stata software (version 12.0, Stata Corp LP, College Station, TX). International Journal of Neuroscience
Int J Neurosci Downloaded from informahealthcare.com by Dicle Univ. on 11/16/14 For personal use only.
eNOS T-786C polymorphism and ischemic stroke
645
Figure 3. Forest plot of IS risk associated with the eNOS T-786C polymorphism stratified by ethnicity. CC + TC vs. TT model by the fixed effects for each of the 12 published studies. For each study, the estimates of OR and its 95% CI were plotted with a box and a horizontal line. The symbol filled diamond indicates pooled OR and its 95% CI. No significant association of the eNOS T-786C polymorphism with IS risk was found.
Results Study characteristics We identified a total of 87 relevant publications that matched our search terms at initial screening. After excluding the studies that did not satisfy the inclusion criteria, 12 publications [19–22, 27–34] were included in the present meta-analysis (Figure 1). The data collected from the eligible studies are summarized in Table 1. Since the study by Howard et al. [20] included two independent study groups with different ethnicities, which were treated separately and divided into Caucasian and African-American. Therefore, the meta-analysis finally included 13 studies with 2836 IS cases and 3354 con C
2014 Informa Healthcare USA, Inc.
trol subjects. The ethnicity of eligible subjects involved populations ranging from African-American (n = 1), Caucasian (n = 3) and Asian (n = 9). Only one [29] of the 13 studies was slightly deviated from HWE.
Quantitative synthesis The main results of meta-analysis and heterogeneity were listed in Table 2. Two of the five models suggested remarkable between-study heterogeneity, thus both fixed effects model and random effects model were performed to calculate the pooled estimates. Overall, no significant association between T-786C polymorphism and IS was observed under all genetic models (Figures 2–4).
646
UK USA USA China Singapore Turkey India Bahraini Korea Korea China China China
Hassan (2004) Howarda (2005) Howardb (2005) Cheng (2008) Moe (2008) Yemici (2009) Majumdar (2010) Saidi (2010) Kim (2010) Song (2010) Yan (2011) Li (2011) Meng (2012)
Caucasian African-American Caucasian Asian Asian Caucasian Asian Asian Asian Asian Asian Asian Asian
Ethnicity F/M F F F/M F/M F/M F/M F/M F/M F/M F/M F/M F/M
Gender
Study size 298 50 50 309 120 67 129 329 223 265 558 300 138
Mean age 67.10 ± 10.26 39 39 61.34 ± 10.26 62.5 ± 1.1 63.5 ± 10.5 29.71 ± 10.82 61.8 ± 12.2 61.84 62.22 ± 11.90 61.0 ± 9.8 61.57 ± 5.82 67.6 ± 10.9 115 39 20 240 86 25 70 162 186 218 434 230 124
TT
, :different ethnicities in one study; F/M: female/male; Hardy-Weinberg equilibrium (HWE).
a b
Country 143 11 20 58 27 33 50 131 37 43 122 66 14
TC
Case
40 0 10 11 7 9 9 36 0 4 2 4 0
CC 373 89 60 538 199 83 190 455 409 479 990 526 262
T 223 11 40 80 41 51 68 203 37 51 126 74 14
C
599 75 117 309 207 79 129 444 206 232 557 300 100
Study size
220 42 40 250 152 35 69 249 171 193 451 238 90
TT
Characteristics of studies included in the meta-analysis for an association between the eNOS T-786C polymorphism and IS risk.
First author (year)
Table 1.
Int J Neurosci Downloaded from informahealthcare.com by Dicle Univ. on 11/16/14 For personal use only.
283 27 59 56 52 41 55 162 35 39 96 57 10
TC
96 6 18 3 3 3 5 33 0 0 10 5 0
CC
Control
723 111 139 556 356 111 193 660 377 425 998 533 190
T
475 39 95 62 58 47 65 228 35 39 116 67 10
C
Y Y Y Y Y N Y Y Y Y Y Y Y
HWE
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Ph
0.97 (0.78, 1.21) 0.85 (0.63, 1.16) 1.13 (0.99, 1.28) 1.05 (0.95, 1.17)
0.921 0.314 0.999 0.912
0.98 (0.81, 1.19) 0.846 0.50 (0.23, 1.08) NA 1.11 (0.98, 1.26) 0.998
OR (95% CI)
CC + TC vs. TT
0.0% 13.6% 0.0% 0.0%
0.0% NA 0.0%
I
2
Ph
0.84 (0.56, 1.24) NA 1.18 (0.46, 3.00) 0.203 1.71 (0.82, 3.54) 0.028 1.36 (0.85, 2.18) 0.013
1.25 (0.63, 2.49) 0.104 0.12 (0.01, 2.09) NA 1.55 (0.79, 3.03) 0.046
OR (95% CI)
CC vs. TC + TT I
2
NA 37.3% 57.6% 55.7%
55.9% NA 53.1%
Ph : pvalue of heterogeneity test; NA: not available; CI: confidence interval; OR, odds ratio; NA: not available.
NA 30.1% 54.0% 62.5%
0.39 (0.26, 0.58) NA 0.57 (0.24, 1.37) 0.239 1.13 (0.56, 2.27) 0.042 0.79 (0.47, 1.32) 0.003
I 45.4% NA 52.5%
Ph
2
0.53 (0.29, 0.98) 0.160 0.07 (0.00, 1.35) NA 1.05 (0.54, 2.05) 0.049
OR (95% CI)
CC vs. TT
Meta-analysis of the associations between the eNOS T-786C polymorphism and IS risk.
Ethnicity Caucasian African-American Asian Mean age >65
