Dataset Information

The association of four common polymorphisms from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity: a meta-analysis.

ABSTRACT:

Objective

Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity. To generate more information, we aimed to evaluate the association of four common polymorphisms (rs3842787, rs20417, rs201184269, rs1126643) from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity via a meta-analysis.

Methods and results

In total, there were 4 (353/595), 6 (344/698), 10 (588/878) and 7 (209/676) articles (patients/controls) qualified for rs3842787, rs20417, rs20118426 and rs1126643, respectively. The data were extracted in duplicate and analyzed by STATA software (Version 11.2). The risk estimate was expressed as odds ratio (OR) and 95% confidence interval (95% CI). Analyses of the full data set indicated significant associations of rs20417 (OR; 95% CI; P: 1.86; 1.44-2.41; <0.0005) and rs1126643 (2.37; 1.44-3.89; 0.001) with aspirin insensitivity under allelic model. In subgroup analyses, the risk estimate for rs1126643 was greatly potentiated among patients with aspirin semi-resistance relative to those with aspirin resistance, especially under dominant model (aspirin semi-resistance: 5.44; 1.42-20.83; 0.013 versus aspirin resistance: 1.96; 1.07-3.6; 0.03). Further grouping articles by ethnicity observed a stronger prediction of all, but rs20417, examined polymorphisms for aspirin insensitivity in Chinese than in Caucasians. Finally, meta-regression analyses observed that the differences in percentage of coronary artery disease (P?=?0.034) and averaged platelet numbers (P?=?0.012) between two groups explained a large part of heterogeneity for rs20417 and rs1126643, respectively.

Conclusion

Our findings provide strong evidence that COX-2 and ITGA2 genetic defects might increase the risk of having aspirin insensitivity, especially for aspirin semi-resistance and in Chinese populations.

SUBMITTER: Weng Z

PROVIDER: S-EPMC3828324 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The association of four common polymorphisms from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity: a meta-analysis.

Weng Zhiyuan Z Li Xiaobo X Li Yuqiong Y Lin Jinxiu J Peng Feng F Niu Wenquan W

PloS one 20131114 11

<h4>Objective</h4>Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity. To generate more information, we aimed to evaluate the association of four common polymorphisms (rs3842787, rs20417, rs201184269, rs1126643) from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity via a meta-analysis.<h4>Methods and results</h4>In total, there were 4 (353/595), 6 (344/698), 10 (588/878) and 7 (209/676) articles (patients/controls) qualifie ...[more]

PMID: 24244288

Similar Datasets

Project description:Numerous studies have investigated the relationship between various candidate gene polymorphisms and gallbladder stone disease (GSD) across ethnic populations; however, the results are often inconsistent. This meta-analysis aims to comprehensively evaluate the influence of common ABCG8 T400K, ABCG8 D19H, ABCG8 C54Y, ApoB100 EcoRI, ApoB100 XbaI, ApoE HhaI, CETP TaqI, CYP7A1 Bsa, LRPAP1 I/D and TNF-α A308G polymorphisms on the risk of gallbladder stone disease. 33 Full-text articles with 9250 cases and 12,029 healthy controls (total 21,279 subjects) were analyzed using the RevMan software (V5.1) and the Comprehensive Meta-analysis software (Version 2.0, BIOSTAT, Englewood, NJ) a Random-effects model was applied. Begg's funnel plots, Fail-safe number, Egger's regression intercept and Begg and Mazumdar rank correlation tests were performed for the potential publication bias and sensitivity analysis. The studies were also sub-grouped into European and non-European groups to find out role of ethnicity, if any, on GSD risk. Studies included in quantitative synthesis were ABCG8 T400K rs4148217 (cases/controls, n = 671/1416) (4 studies), ABCG8 D19H rs11887534 (n = 1633/2306) (8 studies), ABCG8 C54Y rs4148211 (n = 445/1194) (3 studies), ApoB100 EcoRI rs1042031 (n = 503/390) (4 studies), ApoB100 XbaI rs693 (n = 1214/1389) (9 studies), ApoE HhaI rs429358 (n = 1335/1482) (12 studies), CETP TaqI rs708272 (n = 1038/1025) (5 studies), CYP7A1 Bsa rs3808607 (n = 565/514) (3 studies), LRPAP1 I/D rs11267919 (n = 849/900) (3 studies), TNF-α A308G rs1800629 (n = 997/1413) (3 studies). The combined results displayed significant association of ABCG8 D19H (GC + CC) [OR with 95%CI = 2.2(1.7-2.8); p < 0.00001], ABCG8 Y54C (GA + GG) [OR with 95%CI = 0.65(0.5-0.9); p = 0.01]. APOB100 EcoRI (GG vs. AA) [OR with 95%CI = 0.51(0.3-0.9); p = 0.05], (GG vs. GA) [OR with 95%CI = 0.6(0.4-0.9); p = 0.04], (GA + AA) [OR with 95%CI = 0.6(0.4-0.9); p = 0.006]. APOB Xba I (X- vs. X+) [OR with 95%CI = 0.53(0.3-0.8); p = 0.006. APOE Hha I (E4/E4 vs. E3/E3) [OR with 95%CI = 3.5(1.1-14.9); p = 0.04] and LRPAP1 I/D (ID + II) [OR with 95%CI = 1.27(1.0-1.6); p = 0.03] with the GSD risk. It was found that ABCG D19H was significantly associated with GSD in both European and Non-European populations. While APOB XbaI and LRPAP1 I/D markers were associated with gallstone disease only in Non- European population. Additionally, APOE HhaI and APOB 100 ECoRI were found to be associated with GSD only in European population. The results of quantitative synthesis suggest that the ABCG8 D19H polymorphism was associated with the increased risk of GSD in both European and Non-European populations, APOE Hha I and LRPAP1 I/D polymorphisms were associated with the increased risk of GSD in European and Non-European population respectively. However, no association was found in ABCG8 T400K, CETP Taq1, CYP7A1 Bsa and TNF-A308G polymorphisms with Gallstone Disease.

Project description:BackgroundWhether aspirin use can decrease or increase cancer risk remains controversial. In this study, a meta-analysis of cohort studies and randomized controlled trials (RCTs) were conducted to evaluate the effect of aspirin use on common cancer risk.MethodMedline and Embase databases were searched to identify relevant studies. Meta-analyses of cohort studies and RCTs were performed to assess the effect of aspirin use on the risk of colorectal, gastric, breast, prostate and lung cancer. Cochran Q test and the I square metric were calculated to detect potential heterogeneity among studies. Subgroup meta-analyses according to exposure categories (frequency and duration) and timing of aspirin use (whether aspirin was used before and after cancer diagnosis) were also performed. A dose-response analysis was carried out to evaluate and quantify the association between aspirin dose and cancer risk.ResultsA total of 88 cohort studies and seven RCTs were included in the final analysis. Meta-analyses of cohort studies revealed that regular aspirin use reduced the risk of colorectal cancer (CRC) (RR=0.85, 95%CI: 0.78-0.92), gastric cancer (RR=0.67, 95%CI: 0.52-0.87), breast cancer (RR=0.93, 95%CI: 0.87-0.99) and prostate cancer (RR=0.92, 95%CI: 0.86-0.98), but showed no association with lung cancer risk. Additionally, meta-analyses of RCTs showed that aspirin use had a protective effect on CRC risk (OR=0.74, 95%CI: 0.56-0.97). When combining evidence from meta-analyses of cohorts and RCTs, consistent evidence was found for the protective effect of aspirin use on CRC risk. Subgroup analysis showed that high frequency aspirin use was associated with increased lung cancer risk (RR=1.05, 95%CI: 1.01-1.09). Dose-response analysis revealed that high-dose aspirin use may increase prostate cancer risk.ConclusionsThis study provides evidence for low-dose aspirin use for the prevention of CRC, but not other common cancers. High frequency or high dose use of aspirin should be prescribed with caution because of their associations with increased lung and prostate cancer risk, respectively. Further studies are warranted to validate these findings and to find the minimum effective dose required for cancer prevention.

Dataset Information

The association of four common polymorphisms from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity: a meta-analysis.

Objective

Methods and results

Conclusion

Publications

The association of four common polymorphisms from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity: a meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure