Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
J Hum Genet. 2011 Mar;56(3):211-6. doi: 10.1038/jhg.2010.169. Epub 2011 Jan 13.
Genetic factors are known to have an important role in intracranial aneurysm (IA) pathogenesis. The purpose of this study is to identify single-nucleotide polymorphisms (SNPs) that are associated with IA in Japanese population. A total of 2050 IA patients and 1835 controls recruited in Biobank Japan, The University of Tokyo were used in this study. In all, 45 SNPs in 24 genes encoding proteins, which have been considered to be possible risk factors to IA pathogenesis, were genotyped using multiplex PCR-invader assay. Association analysis was evaluated by logistic regression analysis before and after adjustment of age, smoking and hypertension status. This case-control association study revealed a SNP, rs6460071 located on LIMK1 gene (P = 0.00069) to be significantly associated with increased risk of IA. In addition, two SNPs, rs243847 (P = 0.00086) and rs243865 (P = 0.00090), on matrix metallopeptidase 2 (MMP2) gene and one SNP rs1799724 (P = 0.0026) on tumor necrosis factor-α (TNF-α) gene, are marginally associated with IA in male- and female-specific manner, respectively. In conclusion, a large-scale case-control association study was conducted to verify genetic variations associated with IA in Japanese population. This study gave insights on the importance of stratified analysis between genders, and suggested that the underlying mechanism of IA pathogenesis might differ between females and males.
遗传因素被认为在颅内动脉瘤（IA）发病机制中起着重要作用。本研究旨在鉴定与日本人群中 IA 相关的单核苷酸多态性（SNP）。本研究使用了日本生物银行、东京大学招募的 2050 名 IA 患者和 1835 名对照。总共对 24 个编码蛋白的基因中的 45 个 SNP 进行了基因分型，这些基因被认为是 IA 发病机制的可能风险因素，使用多重 PCR-入侵检测法。在调整年龄、吸烟和高血压状况后，通过逻辑回归分析评估了关联分析。这项病例对照关联研究显示，位于 LIMK1 基因上的 SNP rs6460071（P = 0.00069）与 IA 风险增加显著相关。此外，MMP2 基因上的两个 SNP rs243847（P = 0.00086）和 rs243865（P = 0.00090）以及 TNF-α 基因上的 SNP rs1799724（P = 0.0026）在男性和女性中分别以性别特异性的方式与 IA 呈边缘相关。总之，进行了一项大规模的病例对照关联研究，以验证与日本人群中 IA 相关的遗传变异。本研究深入了解了性别分层分析的重要性，并表明 IA 发病机制的潜在机制在女性和男性之间可能存在差异。
