ARHGEF7遗传变异与颅内动脉瘤相关

Association of ARHGEF7 genetic variants with intracranial aneurysm

目的探讨Rho鸟嘌呤核苷酸交换因子7(ARHGEF7)基因遗传变异与颅内动脉瘤形成和破裂风险的关系。方法收集颅内动脉瘤患者121例(包括未破裂组患者41例,破裂组患者80例)和健康对照155名,检测ARHGEF7的10个遗传变异。利用logistic回归模型分析ARHGEF7遗传变异与颅内动脉瘤发生和破裂风险的关系。结果在校正年龄、性别和传统心血管危险因素后,与rs4145274GG基因型相比,rs4145274GA与颅内动脉瘤破裂风险降低相关,比值比为0.24[95%可信区间(CI):0.09~0.69,P<0.05];与rs1555751CC基因型相比,rs1555751CT与颅内动脉瘤破裂风险降低也相关,比值比为0.17(95%CI:0.05~0.63,P<0.05)。rs4145274和rs1555751的联合效应提示患者遗传风险评分越高,颅内动脉瘤破裂风险越低,比值比为0.14(95%CI:0.04~0.55,P<0.05)。结论ARHGEF7遗传变异可能是颅内动脉瘤破裂风险的遗传标记。

Objective To identify the relationship between Rho guanine nucleotide exchange factor 7(ARHGEF7)genetic variants and the formation and rupture risk of intracranial aneurysms.Methods Ten variants of the ARHGEF7 were detected in a case-control study which included 121 patients with intracranial aneurysms(including 41 unruptured and 80 ruptured patients)and 155 healthy controls.The relationship between variants and occurrence and rupture risk of intracranial aneurysms was examined by multivariate logistic regression model.Results After adjustment for age,sex,and traditional cardiovascular risk factors,the rs4145274GA genotype was associated with a decreased rupture risk of intracranial aneurysms as compared with rs4145274GG genotype,and odds ratio was 0.24[95%confidence interval(CI):0.09~0.69,P<0.05].The rs1555751CT genotype was also associated with a decreased rupture risk of intracranial aneurysms as compared with rs1555751CC genotype,and odds ratio was 0.17(95%CI:0.05~0.63,P<0.05).The combined effect rs4145274 and rs1555751 suggested that the patients with an increased genetic risk score had a lower rupture risk of intracranial aneurysms,and the odds ratio was 0.14(95%CI:0.04~0.55,P<0.05).Conclusions The study indicates that ARHGEF7 genetic variants potentially serve as potential genetic markers for the risk evaluation of ruptured intracranial aneurysms.