Variants of the Arachidonate 5-Lipoxygenase-Activating Protein (ALOX5AP) Gene and Risk of Stroke: A HuGE Gene-Disease Association Review and Meta-Analysis

Abstract

Variants of the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene have been implicated as a risk factor for stroke. However, genetic association studies that have examined the association between ALOX5AP gene variants (HapA haplotype, HapB haplotype, and SG polymorphisms) and stroke have produced conflicting results. Therefore, the authors performed a meta-analysis of all studies with ALOX5AP genotyping (5,194 stroke cases and 4,566 controls). The meta-analysis showed significant heterogeneity among studies (P(Q) = 0.03, I(2) = 63%) and a nonsignificant association between the HapA haplotype (SG13S25G-SG13S114T-SG13S89G-SG13S32A) and stroke risk (random-effects (RE) odds ratio (OR) = 1.13, 95% confidence interval (CI): 0.88, 1.45). Regarding the HapB haplotype (SG13S377A-SG13S114A-SG13S41A-SG13S35G), there was no association with stroke risk (RE OR = 1.03, 95% CI: 0.77, 1.37). The SG13S114, SG13S89, SG13S25, SG13S32, SG13S35, and SG13S42 polymorphisms were not associated with stroke. The SG13S106 and SG13S377 polymorphisms revealed evidence of marginal association (RE OR = 1.23 (95% CI: 1.03, 1.46) and RE OR = 1.25 (95% CI: 1.04, 1.50), respectively). However, cumulative meta-analysis for the HapA haplotype showed a downward trend of odds ratios over time, and recursive cumulative meta-analysis indicated insufficient evidence for claiming or denying an association. Tests for bias revealed no evidence of biases. Rigorous genetic association studies investigating gene-gene-environment interactions may generate more conclusive claims about the genetics of stroke.