Dataset Information

The roles of ANRIL polymorphisms in coronary artery disease: a meta-analysis.

ABSTRACT: BACKGROUND:The relationship between antisense non-coding RNA (ncRNA) in the INK4 locus (ANRIL) polymorphisms and coronary artery disease (CAD) remains inconclusive. Thus, we conducted this meta-analysis to better evaluate the roles of ANRIL polymorphisms in CAD. METHODS:Systematic literature search of PubMed, Medline, and Embase was performed to identify potential relevant articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of association. RESULTS:Fifteen studies were finally enrolled for analyses. Overall analyses suggested that rs1333040 (dominant model: P<0.0001; recessive model: P<0.0001; allele model: P<0.0001), rs1333049 (dominant model: P=0.02; allele model: P=0.02) and rs2383207 (additive model: P=0.004) polymorphisms were significantly associated with the risk of CAD. Further subgroup analyses showed that rs1333040, rs1333049, and rs2383207 polymorphisms were significantly correlated with the risk of CAD in East Asians, rs2383206 and rs10757274 polymorphisms were significantly correlated with the risk of CAD in West Asians, while rs2383206, rs10757274, and rs10757278 polymorphisms were significantly correlated with the risk of CAD in Caucasians. CONCLUSION:Our findings indicated that rs1333040, rs1333049, rs2383206, rs2383207, rs10757274, and rs10757278 polymorphisms might serve as genetic biomarkers of CAD in certain ethnicities.

SUBMITTER: Hu L

PROVIDER: S-EPMC6923330 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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The roles of ANRIL polymorphisms in coronary artery disease: a meta-analysis.

Hu Lina L Su Guoyi G Wang Xia X

Bioscience reports 20191201 12

<h4>Background</h4>The relationship between antisense non-coding RNA (ncRNA) in the INK4 locus (ANRIL) polymorphisms and coronary artery disease (CAD) remains inconclusive. Thus, we conducted this meta-analysis to better evaluate the roles of ANRIL polymorphisms in CAD.<h4>Methods</h4>Systematic literature search of PubMed, Medline, and Embase was performed to identify potential relevant articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of as ...[more]

PMID: 30814313

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Project description:Genetic variations that influence DNA repair efficiency may contribute to coronary artery disease (CAD) susceptibility. Previous studies have investigated whether there was evidence of an association between polymorphisms at the X-ray repair cross complementing 1 (XRCC1) gene and susceptibility to CAD, but findings have been inconclusive. We identified eligible studies through a comprehensive literature search to determine whether an association exists between XRCC1 gene polymorphisms and CAD susceptibility. Findings were assessed using the odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed- or random-effects model, based on the heterogeneity of the studies. Ten eligible studies were finally included in this meta-analysis. Our pooled analysis found that XRCC1 polymorphisms were significantly associated with CAD susceptibility under recessive (Arg194Trp: OR = 1.47, 95% CI = 1.13-1.93; Arg399Gln: OR = 1.45, 95% CI = 1.12-1.89), homozygous (Arg194Trp: OR = 1.37, 95% CI = 1.03-1.81; Arg399Gln: OR = 1.56, 95% CI = 1.19-2.05), and allele (Arg399Gln: OR = 1.18, 95% CI = 1.06-1.32) genetic models. Following subgroup analysis by ethnicity, in Asian populations, we found evidence of associations between the XRCC1 Arg194Trp polymorphism and CAD under recessive and homozygous genetic models, and between the XRCC1 Arg399Gln polymorphism and CAD under recessive, homozygous, and allele genetic models. Subgroup analysis stratified by control source revealed associations between the Arg194Trp and Arg399Gln polymorphisms and susceptibility to CAD under recessive and homozygous modes of inheritance, respectively. In addition, subgroup analysis stratified by sample size found that findings of the Arg194Trp polymorphism in large sample sizes were comparable to those found using pooled eligible studies. Based on our meta-analysis, we concluded that the XRCC1 gene polymorphisms, Arg194Trp and Arg399Gln, are associated with CAD susceptibility, specifically in Asian populations. However, additional, comprehensive and well-designed studies are warranted to confirm these findings.

Project description:BackgroundThe selectins play important roles in the inflammatory process of coronary artery disease (CAD) and myocardial infarction (MI). Previous studies have shown ambiguous findings regarding a possible association between the selectin genes and CAD. The E-selectin Ser128Arg polymorphism and the P-selectin Thr715Pro polymorphism have been investigated widely but with inconsistent results. We performed a comprehensive meta-analysis to shed light on this issue.MethodsData were extracted by searches of MEDLINE, Embase, CNKI, Wanfang, Google Scholar, PORTA, GeNii, CiNii, J-STAGE, Nurimedia and Koreanstudies Information Service System [Kiss] up to October 2013, in which 10 studies on the Ser128Arg polymorphism with 3369 cases and 2577 controls and 10 studies on the Thr715Pro polymorphism with 5886 cases and 18345 controls. A random-effects model was used to calculate the combined odds ratios. The between-study heterogeneity and publication bias were addressed.ResultsThe 128Arg carriers had a significant increased risk of CAD (allele comparison: P = 0.02, OR = 1.33, 95%CI 1.04-1.69, P(heterogeneity) = 0.01); The 715Pro conferred a non-significant risk reduction relative to the 715Thr (allele comparison: P = 0.40, OR = 0.94, 95%CI 0.82-1.08, P(heterogeneity) = 0.03).Subgroup analyses demonstrated that the 128Arg carriers had a significant increased risk of CAD among Asians (allele comparison: P = 0.001, OR = 2.07, 95%CI 1.33-3.24, P(heterogeneity) = 0.77) but not among Caucasians (allele comparison: P = 0.33, OR = 1.13, 95%CI 0.88-1.45, P(heterogeneity) = 0.08). Carrier status for the 715Pro was significantly associated with reduced risk of MI (allele comparison: P = 0.04, OR = 0.81, 95%CI 0.67-0.99, P(heterogeneity )= 0.14). The asymmetric funnel plot and the Egger's test (P = 0.041) suggested the presence of publication bias for the Ser128Arg polymorphism.ConclusionOur results suggested there is an increase in the risk of CAD conferred by the Ser128Arg polymorphism and the thr715Pro polymorphism may be a protective factor of MI.

Project description:BackgroundBoth DNA genotype and methylation of antisense non-coding RNA in the INK4 locus (ANRIL) have been robustly associated with coronary artery disease (CAD), but the interdependent mechanisms of genotype and methylation remain unclear.MethodsEighteen tag single nucleotide polymorphisms (SNPs) of ANRIL were genotyped in a matched case-control study (cases 503 and controls 503). DNA methylation of ANRIL and the INK4/ARF locus (p14ARF, p15INK4b and p16INK4a) was measured using pyrosequencing in the same set of samples (cases 100 and controls 100).ResultsPolymorphisms of ANRIL (rs1004638, rs1333048 and rs1333050) were significantly associated with CAD (p < 0.05). The incidence of CAD, multi-vessel disease, and modified Gensini scores demonstrated a strong, direct association with ANRIL gene dosage (p < 0.05). There was no significant association between ANRIL polymorphisms and myocardial infarction/acute coronary syndrome (MI/ACS) (p > 0.05). Methylation levels of ANRIL were similar between the two studied groups (p > 0.05), but were different in the rs1004638 genotype, with AA and AT genotype having a higher level of ANRIL methylation (pos4, p = 0.006; pos8, p = 0.019). Further Spearman analyses indicated that methylation levels of ANRIL were positively associated with systolic blood pressure (pos6, r = 0.248, p = 0.013), diastolic blood pressure (pos3, r = 0.213, p = 0.034; pos6, r = 0.220, p = 0.028), and triglyceride (pos4, r = 0.253, p = 0.013), and negatively associated with high-density lipoprotein cholesterol (pos2, r = - 0.243, p = 0.017). Additionally, we identified 12 transcription factor binding sites (TFBS) within the methylated ANRIL region, and functional annotation indicated these TFBS were associated with basal transcription. Methylation at the INK4/ARF locus was not associated with ANRIL genotype.ConclusionsThese results indicate that ANRIL genotype (tag SNPs rs1004638, rs1333048 and rs1333050) mainly affects coronary atherosclerosis, but not MI/ACS. There may be allele-related DNA methylation and allele-related binding of transcription factors within the ANRIL promoter.

Project description:Coronary artery disease (CAD) is a disease which has become a leading cause of death worldwide. The polymorphisms in Interleukin-17 (IL-17A), including rs2275913, rs3819024, rs3819025, rs3748067, rs8193037, rs4711998, and rs8193036, have been found to be probably associated with the risk of CAD. However, the results were inconsistent and inconclusive. The present study performed a meta-analysis to get a more precise and comprehensive estimation of the association between the IL-17A polymorphisms and CAD risk. The Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Databases were searched for related studies. A total of six studies, including 3542 cases and 3212 controls, were identified for the meta-analysis. The main findings of the present meta-analysis show that the TT genotype of IL-17A rs3748067 is associated with a significant lower risk of CAD in the homozygous model odds ratio (OR) (OR = 0.37) in Asians. No significant association was found for rs2275913, rs3819024, rs3819025, rs8193037, rs4711998, and rs8193036 with CAD susceptibility in the overall analysis. However, subgroup analysis indicated a significant decreased risk of CAD for the GG genotype and G allele of rs2275913 in a small sample size group, and a higher risk of CAD for the GG genotype and G allele of rs8193037 in a heterozygous model (OR = 1.56), dominant model (OR = 1.54), and allelic model (OR = 1.47) in Asians. In conclusion, the current meta-analysis suggests a significant relationship between rs3748067, rs8193037, and CAD in Asians, while for rs2275913, rs3819024, rs3819025, rs4711998, rs8193036, no such relations were found. Thus, IL-17A rs3748067 and rs8193037 might be recommended as a predictor for susceptibility of CAD for Asians. However, the results of this meta-analysis are hypothesis-generating results which should be interpreted with caution because of the heterogeneity and publication bias among study designs.

Dataset Information

The roles of ANRIL polymorphisms in coronary artery disease: a meta-analysis.

Publications

The roles of ANRIL polymorphisms in coronary artery disease: a meta-analysis.

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