Abstract: ObjectiveTo determine the association of polymorphism of arachidonate 5-lipoxygenase activating protein(ALOX5AP)gene with ischemic stroke(IS)and its subtypes in discordant sib pairs. MethodsIschemic stroke cases were enrolled from a hospital based stroke registry and discordant sib pairs were recruited by using proband-initiated enrollment.Participants' information and blood samples were collected through community-based health care networks in rural areas of China.Five single nucleotide polymorphism(SNPs)of ALOX5AP were selected:rs10507391,rs9551963,rs12429692,rs4293222,and rs4360791.Generalized estimating equation(GEE)was applied to adjust for within family correlation in the analysis of discordant sib pairs.Family based association test(FBAT)was used to test associations of ALOX5AP gene with ischemic stroke and its subtypes. ResultsTotally 446 discordant sib pairs from 240 ischemic stroke patient pedigrees were analyzed. Resultsof GEE showed that diabetes mellitus,hypertension,diastolic blood pressure level,triglyceride level and high density lipoprotein cholesterol level were associated with ischemic stroke(P<0.05).By the use of FBAT,we found rs9551963A allele and rs4360791A allele in ALOX5AP gene were associated with ischemic stroke(Z=-2.50,-2.52,P<0.05),large-artery atherosclerosis stroke(LAA)(Z=-2.16,-2.27,P<0.05),and diabetes mellitus(Z=-2.33,-2.51,P<0.05)under dominate model,and with small-artery occlusion stroke(SAO)(Z=-2.38,2.08,P<0.05)and hyperlipidemia(Z=-2.63,2.73,P<0.05)under additive model.Rs12429692A allele was associated with small-artery occlusion stroke(Z=2.27,P=0.02)and rs4360791A was associated with hypertension(Z=2.19,P=0.03)under dominate model. ConclusionALOX5AP gene polymorphism is associated with ischemic stroke and its subtypes.