| Objective: Ischemic stroke(IS)is a complex disease that poses a serious threat to human health.It is influenced by a combination of many factors.Several studies have shown that genetic factors play an important role in its occurrence and development.And the genetic variant rs556621 in the intergenic region of Chromosome 6p21.1 may be one of them.The findings of published studies on the association between variant rs556621 and the risk of IS and its major subtype--large artery atherosclerosis(LAA)in Chinese populations are inconsistent.Therefore,we evaluated the association of rs556621 with IS/LAA in Chinese populations by meta-analysis,in order to provide a theoretical basis for the research on the genetic mechanism and clinical prevention and treatment strategies of IS/LAA.Methods: In this study,literature retrieval was conducted in four Chinese databases,namely,Weipu,China National Knowledge Infrastructure(CNKI),Chinese Biomedical(CBM)and Wanfang Databases,with a combination of the Chinese terms including "rs556621","6p21.1","中风","缺血性脑卒中","梗塞","缺血","梗死" and their synonyms;and in four English databases,namely,Pub Med,Embase,ISI Web of Science and the Public Health Genomics and Precision Health Knowledge Base(PHGKB)with a combination of the English terms including "rs556621","6p21.1",“stroke”,“infarction”,“ischemia”,and their synonyms.Literatures were collected from the earliest collection date of each database to September 2,2021.The meta-analysis was performed using STATA software(version 11.0).The analysisprocedures included pooled analysis of effect sizes,heterogeneity test,meta-regression analysis,sensitivity analysis and evaluation of publication bias.Results: 1.According to the literature selection criteria,a total of 10 studies from the Chinese populations were finally included,involving 3,644 IS cases and 3,692 controls(including 7 studies involving 2,268 LAA cases and 2,268 controls)for this meta-analysis to assess the association of variant rs556621 with the risk of IS/LAA.2.Pooled analysis of effect sizes showed that in the overall population,AA genotype was associated with an increased risk of IS(AA vs.CC: odds ratio(OR)1.19,95% confidence interval(CI)1.03-1.36,P = 0.015;AA vs.CA+CC: OR 1.23,95% CI 1.09-1.39,P = 0.001).Subgroup analysis also showed that rs556621 was associated with the risk of IS in Chinese Han populations(AA vs.CA+CC: OR 1.23,95% CI 1.08-1.39,P = 0.001),and also in other ethnic populations(including Uyghur,Mongolian and Kazakh populations)(CA vs.CC: OR 1.56,95% CI 1.16-2.11,P = 0.004;AA vs.CC: OR 1.54,95% CI 1.04-2.29,P = 0.033;AA+AC vs.CC: OR 1.58,95% CI 1.21-2.05,P = 0.001;A vs.C: OR 1.34,95% CI 1.13-1.59,P = 0.001).Similar results were obtained when we restricted the analysis to LAA subtypes.In the overall population,rs556621 was associated with LAA risk(AA vs.CC: OR 1.24,95% CI 1.14-1.48,P = 0.017;AA vs..CA+CC: OR 1.28,95% CI 1.10-1.49,P = 0.002).In subgroup analysis,it was associated with LAA susceptibility in Chinese Han populations(AA vs.CA+CC: OR 1.28,95% CI 1.08-1.51,P = 0.003)and also in other ethnic populations(CA vs.CC: OR 1.62,95% CI 1.26-2.07,P < 0.001;AA vs.CC: OR 1.61,95% CI 1.08-2.42,P = 0.020;AA+AC vs.CC: OR 1.62,95% CI 1.28-2.05,P < 0.001;A vs.C: OR 1.37,95% CI 1.15-1.63,P < 0.001).However,sensitivity analyses showed that these results were stable in Chinese Han populations but not in other ethnic populations.Conclusion: This is the first meta-analysis on the correlation between rs556621 and the susceptibility of IS/LAA in Chinese populations.It reveals that variant rs556621 is associated with the risk of IS/LAA in Chinese populations.This study provides pooled data to better understand the association between rs556621 and IS/LAA risk in Chinese populations,although the sample size is not large enough.Therefore,in the future,multi-ethnic studies with larger sample sizes are needed to detect this effect. |
PDF Full Text Request