CDKN2A和CDKN2B区域间的基因多态性与汉族人群颅内动脉瘤性别差异性的关联分析  

Association Analysis of Genetic Polymorphisms of CDKN2A-CDKN2B Region with Gender Differential Effect on Intracranial Aneurysm in Chinese Han Population

作　　者：欧阳嶷[1] 阎雪晶[1] 刘颖[1] 张婧[1] OUYANG Yi;YANXue-jing;LIU Ying;ZHANG Jing(Department of Neurology,the First Affiliated Hospital,China Medical University,Shenyang,Liaoning,110001,China)

机构地区：[1]中国医科大学附属第一医院神经内科,辽宁沈阳110001

出　　处：《中国血液流变学杂志》2020年第1期16-21,F0002,共7页Chinese Journal of Hemorheology

基　　金：国家自然科学基金资助项目(81100879);辽宁省自然科学基金项目(201602847)。

摘　　要：目的 研究CDKN2A-CDKN2B区域的基因多态性与汉族人群颅内动脉瘤(intracranial aneurysm,IA)的相关性.方法 收集500例中国汉族IA病例作为研究对象,通过病例对照的关联分析方法 和分层分析方法 ,从遗传学角度探讨存在于IA患者的性别差异与上述基因多态性是否存在关联.结果 位于9p21.3的CDKN2A-CDKN2B区域4个与血管疾病相关的SNP位点(rs1333040、rs2891168、rs2383207和rs10757278)中,rs1333040与汉族人群IA发病密切相关,其风险性主要来源于T等位基因(χ2=6.278,P=0.012,OR=1.378,95%CI 1.072~1.771).应用Logistic回归校正性别、年龄及饮酒、吸烟等危险因素后,发现rs1333040位点的T/T基因型及T等位基因是IA的独立危险因素,其患病风险率增加至1.796倍.亚组分析显示rs2891168的A/A基因型与前循环分布区的IA密切相关(P=0.025).在按性别进行统计的亚组分析中,rs1333040 T/T基因型与汉族男、女IA发病均密切相关,但与女性IA的关联程度更高.结论 遗传因素和性别在IA的发生中具有一定的影响作用.Objective To study the relationship between CDKN2A-CDKN2B genetic polymorphisms and intracranial aneurysm(IA)in Chinese Han population.Methods 500 Chinese Han patients with IA were selected as the research objects in this study.Case-control association analysis and hierarchical analysis were used to assess the associations of four polymorphisms in the CDKN2A-CDKN2B region with IA.Furthermore,to examine the sex-specific effect,we elucidated the above significant associations of candidate SNPs and IA phenotypes with gender stratification.Results This study confirmed that among the four SNPs(rs 1333040,rs289116&rs2383207 and rsl0757278)located in the CDKN2A-CDKN2B region of 9p21.3,rs 1333040 is closely associated with IA in Han population,and its risk mainly came from T allele(x^2=6.278,P=0.012,OR=1.378,95%CI1.072-1.771).Furthermore,Logistic regression analysis showed that T/T genotype and T allele of rs 1333040 were independent risk factors of IA,and the risk rate increased to 1.796 times,indicating it might be one of the independent risk factors of IA.In addition,subgroup analysis showed that the A/A genotype of rs2891168 was closely related to IA in anterior circulation distribution region(P=0.025).Sex-specific analysis showed that the significant association of rsl333040 T/T genotypes not only existed in men with IA but also in women,but the association with female IA is higher.Conclusion Genetic factors and gender difference have a certain influence on the occurrence of IA.

关 键 词：CDKN2A-CDKN2B区域 颅内动脉瘤 基因多态性 性别差异 

分 类 号：R743.3[医药卫生—神经病学与精神病学]