Platelet glycoprotein gene Ia C807T, HPA-3, and Ibα VNTR polymorphisms are associated with increased ischemic stroke risk: Evidence from a comprehensive meta-analysis

Abstract

Background/aims Platelet glycoproteins play a crucial role in the initial stage of thrombus formation and may contribute to the pathophysiology of atherosclerosis. Polymorphisms in glycoprotein genes alter the function of the protein, possibly leading to increased risk of ischemic stroke. However, previous genetic association studies that examined the relationship between glycoprotein genes polymorphisms and ischemic stroke have yielded inconsistent results. This study aimed to evaluate the association between glycoprotein genes and ischemic stroke by the application of meta-analysis. Methods Relevant studies were identified by an extensive search through databases. The quality of included studies was assessed independently using the Newcastle–Ottawa Scale. Allele and genotype frequencies for each included study were extracted. The odds ratio (OR) with 95% confidence interval (95%CI) was calculated using a random-effects or fixed-effects model. Q statistic was used to evaluate homogeneity, and a meta-regression model was used to explore the study-level variables and to describe the heterogeneity in included studies. Egger’s test and funnel plot were used to assess publication bias. Results A total of 60 studies (9 polymorphisms) were included and identified in the current meta-analysis. The Newcastle–Ottawa Scale scores ranged from 7 to 9 except for two studies with Newcastle–Ottawa Scale scores of 6. The T allele or TT genotype of the glycoprotein Ia C807T polymorphism were associated with an increased susceptibility to ischemic stroke in combined population (807T allele: OR, 95%CI: 1.24, 1.03–1.50, p = 0.02) or Asian populations (807T allele: OR, 95%CI: 1.31, 1.10–1.54, p = 0.002 and 807TT genotype: OR, 95%CI: 1.53, 1.13–2.08, p = 0.006, respectively), and the Ser allele of HPA-3 was associated with increased risk of ischemic stroke in combined population or in Asians (OR, 95%CI: 1.21, 1.04–1.40, p = 0.01 or 1.54, 1.18–2.01, p = 0.001). Of note, the Ser/Ser genotype was more common in Asians (OR, 95%CI: 2.09, 1.40–3.13, p < 0.001). For glycoprotein Ibα variable number tandem repeat, only B allele showed a mild significant association with ischemic stroke risk in combined population or in Caucasians (OR, 95%CI: 2.17, 1.04–4.55, p = 0.04 or 1.79, 1.02–3.13, p = 0.04). There was no significant association between HPA-1, HPA-2, HPA-4, HPA-5, glycoprotein Ibα-5 T/C as well as Ia G873A polymorphisms and increased risk of ischemic stroke. Conclusions We found that glycoprotein Ia C807T T allele or the TT genotype, the Ser-allele of HPA-3 and B allele of glycoprotein Ibα variable number tandem repeat polymorphisms were associated with increased risk for ischemic stroke. Future studies with larger sample sizes will be necessary to confirm the results. In addition, analyses of ischemic stroke subtypes and gene–gene and gene–environment interactions are warranted.