Gene polymorphisms and risk of adult early-onset ischemic stroke: A meta-analysis

Introduction: Genetic studies restricted to young adult ischemic stroke patients may help in excluding the potentially confounding variables encountered with advanced age; thus, allowing a more precise risk evaluation derived from the inherited mutations alone. Through meta-analysis, this study was conducted to determine the genetic risk contributed by each susceptibility gene polymorphism, particularly in adult early-onset ischemic stroke patients. Materials and Methods: Electronic databases were searched for all the case-control studies relating to any candidate genes for ischemic stroke. The range of age was 18-50 years for cases. Fixed or random effects model was used depending on the heterogeneity between studies. Results: Twenty-six studies were finally included in this meta-analysis; these studies focused on 7 candidate genes. A significant but modest association was identified for 2 polymorphisms, namely, methylenetetrahydrofolate reductase (MTHFR) C677T (OR=1.44, 95% CI=1.14-1.80) and apolipoprotein E (ApoE) epsilon 2-4 (OR=253, 95% CI=1.71-3.73). Although the pooled analysis for platelet glycoprotein a (GPIa) C807T showed a positive association (OR=1.50, 95% CI=1.10-2.05), the Egger's test indicated the existence of publication bias (t=5.27, P>vertical bar t vertical bar=0.034). Conclusions: Genetic abnormalities specific to homocysteine and lipid metabolism increase the risk for ischemic stroke at an early age. These data may offer important implications for future genetic association studies for stroke. (C) 2009 Elsevier Ltd. All rights reserved.