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Association between the interleukin-6 genetic polymorphism 174?G/C and thrombosis disorder risk: Meta-analysis of 10,549 cases and 19,316 controls.

ABSTRACT: Studies investigating the association between interleukin-6 (IL-6) gene-174?G/C polymorphism (rs1800795) and thrombosis disorder risk reported conflicting results. The aim of our study was to assess the association between the IL-6 gene 174?G/C polymorphisms and the risk of thrombosis disorders.Thirty four case-control studies in 29 articles with 29,865 individuals were incorporated in this meta-analysis by searching the public databases including Medline, Embase, and ISI Web of Science databases as of June 1st, 2015. The odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of the association.By pooling all studies, there was marginal association between and the risk of thrombotic disorders (1.09[0.97-1.22]), arterial thrombotic disorders (1.08[0.95-1.23]), and myocardial infarction (MI, 1.14[0.99-1.32]) under dominant genetic effect (C carriers vs GG). In subgroup analyses stratified by ethnicity, study scale, thrombotic category, and country, the results indicated that IL-6 gene-174?G/C polymorphism was significantly associated with increased risk of thrombotic disorders given the conditional such as Asians, large sample-sized, MI, population-based, and Indian studies (C carriers vs GG: 1.39 [1.13-1.72] and C allele vs G allele: 1.36 [1.18-1.56] for Asian; C carriers vs GG: 1.15 [1.01-1.31] and C allele vs G allele: 1.12 [1.01-1.23] for large sample-sized studies; C allele vs G allele: 1.10 [1.03-1.18] for population-based studies; and C carriers vs GG: 1.40 [1.19-1.65] for Indian studies). We did not observe significant association between IL-6-174?G/C and the risk of Caucasians, small sample-sized studies, stroke and venous studies, and other country studies.This meta-analysis suggests that IL-6 gene-174?G/C polymorphism may be marginally associated with risk of thrombotic disorders, arterial disorders, MI especially for Asian, Indian, population-based, and large sample-sized studies. More studies with larger sample size and well-designed studies might be warranted.

SUBMITTER: Ren H

PROVIDER: S-EPMC5058815 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Association between the interleukin-6 genetic polymorphism 174 G/C and thrombosis disorder risk: Meta-analysis of 10,549 cases and 19,316 controls.

Ren Honggang H Zhang Yue Y Yao Yonghua Y Guo Tao T Wang Huafang H Mei Heng H Hu Yu Y

Medicine 20160701 27

Studies investigating the association between interleukin-6 (IL-6) gene-174 G/C polymorphism (rs1800795) and thrombosis disorder risk reported conflicting results. The aim of our study was to assess the association between the IL-6 gene 174 G/C polymorphisms and the risk of thrombosis disorders.Thirty four case-control studies in 29 articles with 29,865 individuals were incorporated in this meta-analysis by searching the public databases including Medline, Embase, and ISI Web of Science database ...[more]

PMID: 27399086

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Project description:IntroductionCirculating IL-6 levels and at least one polymorphic form of IL6 gene (IL6 -174 G/C, rs1800795) have been shown to be independently associated with coronary artery disease (CAD) by several investigators. Despite more than 12 published meta-analyses on this subject, association of -174 G/C with CAD, especially amongst distinct ancestral population groups remain unclear. We, therefore, conducted a systematic review and an updated meta-analysis to comprehensively ascertain the association of IL6 -174 G/C with CAD and circulating IL-6 levels.Materials and methodsRelevant case-control/cohort studies investigating association of -174 G/C with CAD and circulating IL-6 levels were identified following a comprehensive online search. Association status for CAD was determined for the pooled sample, as well as separately for major ancestral subgroups. Association status for circulating IL-6 levels was assessed for the pooled sample, as well as separately for CAD cases and CAD free controls. Study-level odds ratios (OR) and 95% confidence intervals (CI) were pooled using random/fixed-effects model.ResultsQuantitative synthesis for the CAD endpoint was performed using 55 separate qualifying studies with a collective sample size of 51,213 (19,160 cases/32,053 controls). Pooled association of -174 G/C with CAD was found to be statistically significant through dominant (OR 1.15; 95% CI 1.05-1.25, p = 0.002) as well as allelic genetic model comparisons (OR 1.13, 95% CI 1.06-1.21, p = 0.0003). This effect was largely driven by Asian and Asian Indian ancestral subgroups, which also showed significant association with CAD in both genetic model comparisons (OR range 1.29-1.53, p value range ≤ 0.02). Other ancestral subgroups failed to show any meaningful association. Circulating IL-6 levels were found to be significantly higher amongst the 'C' allele carriers in the pooled sample (Standard mean difference, SMD 0.11, 95% CI 0.01-0.22 pg/ml, p = 0.009) as well as in the CAD free control subgroup (SMD 0.10, 95% CI 0.02-0.17 pg/ml, p = 0.009), though not in the CAD case subgroup (SMD 0.17, 95% CI = - 0.02 to 0.37, p = 0.12).ConclusionsThe present systematic review and meta-analysis demonstrate an overall association between IL6 -174 G/C polymorphism and CAD, which seems to be mainly driven by Asian and Asian Indian ancestral subgroups. Upregulation of plasma IL-6 levels in the 'C' allele carriers seems to be at least partly responsible for this observed association. This warrants further investigations with large, structured case-control studies especially amongst Asian and Asian Indian ancestral groups.

Project description:BACKGROUND:Ataxia telangiectasia mutated (ATM) gene plays a key role in response to DNA lesions and is related to the invasion and metastasis of malignancy. Epidemiological studies have indicated associations between ATM rs1801516 polymorphism and different types of cancer, but their results are inconsistent. To further evaluate the effect of ATM rs1801516 polymorphism on cancer risk, we conducted this meta-analysis. METHODS:Studies were identified according to specific inclusion criteria by searching PubMed, Web of Science, and Embase databases. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) under recessive, dominant, codominant, and overdominant models of inheritance were calculated to estimate the association between rs1801516 polymorphism and cancer risk. RESULTS:A total of 37 studies with 12,879 cases and 18,054 controls were included in our study. No significant association was found between rs1801516 polymorphism and cancer risk in overall comparisons (AA vs GG?+?GA: OR?=?0.91, 95% CI, 0.78-1.07; AA+GA vs GG: OR?=?1.00, 95% CI, 0.90-1.11; AA vs GG: OR?=?0.89, 95% CI, 0.75-1.06; GA vs GG: OR?=?1.01, 95% CI, 0.91-1.13; GG?+?AA vs GA: OR?=?1.00, 95% CI, 0.88-1.10). However, after subgroup analyses by region-specified population, significant associations were found in European (AA vs GG?+?GA: OR?=?0.79, 95% CI, 0.65-0.96, P?=?0.017; AA vs GG: OR?=?0.79, 95% CI, 0.65-0.96, P?=?0.017), South American (AA+GA vs GG: OR?=?2.15, 95% CI, 1.37-3.38, P?=?0.001; GA vs GG: OR?=?2.19, 95% CI, 1.38-3.47, P?=?0.001; GG?+?AA vs GA: OR?=?0.46, 95% CI, 0.29-0.72, P?=?0.001), and Asian (AA vs GG?+?GA: OR?=?7.45, 95% CI, 1.31-42.46, P?=?0.024; AA vs GG: OR?=?7.40, 95% CI, 1.30-42.19, P?=?0.024). Subgroup analyses also revealed that compared with subjects carrying a GG genotype, those carrying a homozygote AA had a decreased risk for breast cancer (AA vs GG: OR?=?0.76, 95% CI, 0.59-0.98, P?=?0.035), and the homozygote AA was associated with decreased cancer risk in subjects with family history (AA vs GG: OR?=?0.68, 95% CI, 0.47-0.98, P?=?0.039). CONCLUSIONS:ATM rs1801516 polymorphism is not associated with overall cancer risk in total population. However, for subgroup analyses, this polymorphism is especially associated with breast cancer risk; in addition, it is associated with overall cancer risk in Europeans, South Americans, Asians, and those with family history.

Dataset Information

Association between the interleukin-6 genetic polymorphism 174?G/C and thrombosis disorder risk: Meta-analysis of 10,549 cases and 19,316 controls.

Publications

Association between the interleukin-6 genetic polymorphism 174 G/C and thrombosis disorder risk: Meta-analysis of 10,549 cases and 19,316 controls.

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