Association of TBXA2R, P2Y12 and ADD1 genes polymorphisms with ischemic stroke susceptibility: A metaanalysis

Abstract

Background: Ischemic stroke is a common cause of death and disability throughout the world. We aimed to evaluate the association between polymorphisms in TBXA2R (rs4523, rs768963, rs1131882), P2Y12 (rs204693), ADD1 (rs4961) and risk of ischemic stroke. Methods: A comprehensive retrieval with the databases of Pubmed, Embase, CENTRAL, CNKI and Wan fang data was conducted. The deadline was February 1, 2019. Pooled ORs and 95% CIs were calculated by using the Z-test. Heterogeneity between the included studies was tested using the I2 method. Begg's funnel plot and Egger's linear regression were used to evaluate the publication bias. Software STATA 12.0 (StataCorp, College Station, TX, USA) was used for the meta-analysis and 26 studies with 5,776 cases and 8,025 controls were included. Results: The results indicated significantly higher risk of ischemic stroke associated with TBXA2R variant rs768963 in all genetic models (C vs T: OR=1.27, 95% CI=1.13-1.42, P<0.0001; CC vs TT: OR=1.74, 95% CI=1.36-2.22, P<0.0001; CT vs TT: OR=1.73, 95% CI=1.41, 2.13, P<0.0001; CC+CT vs TT: OR=1.69, 95% CI=1.39-2.06, P<0.0001). Higher risk of ischemic stroke was also found to be associated with P2Y12 variant rs204693 in homozygous model and allelic model (CC vs TT: OR=3.17, 95% CI=1.33-7.55, P=0.009; C vs T: OR=1.47, 95% CI=1.00-2.15, P=0.047). No association was observed for TBXA2R variant rs1131882, rs4523 and ADD1 variant rs4691. Conclusions: The TBXA2R variant rs768963 and P2Y12 variant rs2046934 may be predictive of the risk of ischemic stroke. Further studies with large sample sizes are warranted and should consider both ethnicity and environmental factors.