Association of SOX17 Gene Polymorphisms and Intracranial Aneurysm: A Case-Control Study and Meta-Analysis

BACKGROUND: Genome-wide association studies have revealed an association between SRY-box 17 (SOX17) gene and intracranial aneurysm (IA) formation. However, results were mainly derived from European and Japanese populations. We investigated the association between SOX17 gene polymorphisms and IA in a homogeneous Korean population. We performed a meta-analysis to assess these results in East-Asian populations. METHODS: This cross-sectional study included 187 age-and sex-matched patients with IA and 372 control subjects. Genetic association analysis was performed in the generalized linear model to identify associations between 4 single nucleotide polymorphisms and IA, including 95 patients with ruptured aneurysms and 92 with unruptured aneurysms. The East-Asian meta-analysis of 5100 IA cases and 7930 control cases was conducted under an inverse variance model. RESULTS: Among 4 single nucleotide polymorphisms that passed quality control tests, the minor C allele of rs1072737 was significantly associated with IA (odds ratio 0.69, 95% confidence interval 0.49-0.96, P = 0.03). None of the 4 single nucleotide polymorphisms showed a significant association between patients with ruptured and unruptured aneurysms. Meta-analysis revealed that G alleles of rs10958409 and rs9298506 were significantly associated with IA in the East-Asian population after removing study heterogeneity (odds ratio 1.11, 95% confidence interval 1.04-1.19, P = 0.0023 and odds ratio 1.19, 95% confidence interval 1.07-1.32, P = 0.0016). CONCLUSIONS: Identification of genetic variants located near SOX17 is likely to be clinically significant for IA formation. rs10958409 and rs9298506 may increase risk of IA in East-Asian populations. Our findings may help in the identification of IA pathogenesis.