Chromosome 12p13 variants contribute to large artery atherosclerotic stroke risk in a Chinese population.

Recently, a genome-wide association study (GWAS) identified two common variants (rs12425791 and rs11833579) on Chromosome 12p13 that confer risk for stroke. The aim of this study was to evaluate whether these two variants are associated with risk of large artery atherosclerotic (LAA) stroke in a Chinese population. Rs12425791 and rs11833579 were genotyped using the improved multiple ligase detection reaction in 423 patients with LAA stroke and 423 healthy controls. We found a statistically significantly increased risk of LAA stroke associated with the rs12425791AA genotype (OR=2.28, 95% CI=1.15-4.51) and rs11833579 AA genotype (OR=1.92, 95% CI=1.16-3.15) compared with their GG genotype. When we evaluated these two polymorphisms together, we found that the combined genotypes with 3-4 variant alleles (rs12425791A and rs11833579A) were associated with an increased risk of LAA stroke (OR=2.06, 95% CI=1.26-3.36) compared to 0-2 variants. Moreover, genotype-phenotype correlation analysis showed that rs12425791AA and rs11833579AA carriers had significantly decreased NINJ2 mRNA expression levels in the Chinese population (P=0.003 for rs12425791 and P=0.005 for rs11833579). These results suggested that the rs12425791 and rs11833579 polymorphisms on Chromosome 12p13 may be associated with the risk of LAA stroke and might be used as candidate biomarkers for LAA stroke susceptibility.