OBJECTIVETo investigate the association between polymorphism of leukotriene A4 hydrolase (LTA4H) gene among ischemic stroke patients and the related subtypes in the discordant sib pairs.

METHODSFamilies including ischemic stroke patients and their siblings were recruited. Four single nucleotide polymorphisms (SNPs) of LTA4H as rs2072512, rs2540489, rs2540500 and rs6538697 were selected. Generalized estimating equation (GEE) was used to adjust for in-family correlation in the analysis of discordant sib pairs. Conditional logistic regression model and family based association test (FBAT) were both used to test the associations of LTA4H gene with ischemic stroke and its subtypes.

RESULTSIn total, data from 356 discordant sib pairs from 234 ischemic stroke patient pedigrees were analyzed. Results of GEE showed that hypertension, diabetes mellitus and hyperlipoidemia were associated with ischemic stroke. According to the association test results, rs2540489 G allele was found to be associated with ischemic stroke, both in the additive model (OR = 0.62, 95% CI: 0.41-0.94) and in the recessive model (OR = 0.48, 95% CI: 0.23-1.02). For two main ischemic stroke subtypes, rs2540489 G allele was found to be associated with large-artery atherosclerosis stroke in the additive model (OR = 0.48, 95% CI: 0.24-0.95) and in the recessive model (OR = 0.25, 95% CI: 0.07-0.93). After adjusting age, sex and other factors, the associations mentioned above, still existed.

CONCLUSIONrs2540489 polymorphism in LTA4H gene seemed to be associated with large-artery atherosclerosis stroke.