Genetic Variants in the Transcriptional Regulatory Region of the ALOX5AP gene and Susceptibility to Ischemic Stroke in Chinese Populations

No coding sequence variants of the ALOX5AP gene that lead to amino acid substitutions have been identified. A two-stage study design was used to explore the relationship between variants in the transcriptional regulatory region of ALOX5AP gene and ischemic stroke (IS) risk in Chinese populations. IS was determined using CT and/or MRI. First, 18 SNPs, located in the upstream promoter region of ALOX5AP gene, were genotyped in 200 IS patients and 200 controls. And one potential associated SNP (rs17222919) was identified (P = 0.005,OR = 0.623, 95% CI: 0.448~0.866). Next, another independent case-control cohort comprising 810 IS patients and 825 matched controls was recruited to investigate the role of rs17222919, rs9579646 polymorphisms and their haplotypes in IS risk. The G allele frequency of rs17222919 in the IS group was significantly lower than that in control group (P = 0.007, OR = 0.792, 95% CI: 0.669~0.937). T-A and G-A haplotypes were associated with IS (P = 0.001,OR = 1.282, 95% CI:1.100~1.495; P = 0.0001, OR = 0.712, 95% CI: 0.598~0.848; respectively). Our study providesevidence that rs17222919 is a potential genetic protective factor against IS. Furthermore, the T-A haplotype is a risk factor and the G-A haplotype is a protective factor against IS in Chinese population.