基于基因芯片检测的动脉粥样硬化性心血管疾病高风险人群相关基因分析  

Related gene analysis of atherosclerotic cardiovascular disease high risk population based on gene chip detection

作　　者：郑丽君 钟萍[1] 王忠福 何霞[3] 胡金明 何苗[4] 张清琼[1] 郭建淑[1] ZHENG Lijun;ZHONG Ping;WANG Zhongfu;HE Xia;HU Jinming;HE Miao;ZHANG Qingqiong;GUO Jianshu(Department of Geriatric Cardiology,Sichuan Academy of Medical Sciences&.Sichuan Provin-cial People's Hospital,Chengdu,610072,China;Department of Interventional&Vascular Surgery,Chengdu Intergrated TCM&Western Medicine Hospital;Pharmacogenomics Laboratory,Sichuan Academy of Medical Sciences&Sichuan Provincial People's Hospital;Institute of Blood Transfusion,Chinese Academy of Medical Sciences and Peking Union Medical College)

机构地区：[1]四川省医学科学院·四川省人民医院老年心血管内科,成都610072 [2]成都市中西医结合医院·成都市第一人民医院介入血管外科 [3]四川省医学科学院·四川省人民医院药物基因组实验室 [4]中国医学科学院北京协和医学院输血研究所

出　　处：《临床心血管病杂志》2022年第10期796-800,共5页Journal of Clinical Cardiology

基　　金：2019年四川省医学会高血压疾病(泰阁)专项课题(No:2019TG02)。

摘　　要：目的:通过比较分析动脉粥样硬化性心血管疾病(ASCVD)高风险人群与健康人群相关的基因多态性差异,探讨ASCVD相关的发病机制。方法:选择2019年6月—2020年5月于四川省人民医院心内科门诊和住院治疗的患者,进行总体心血管危险评估,纳入危险分层为极高危和高危患者203例(病例组);另选择同期排除了慢性心脑血管疾病的健康体检者74例(对照组)。提取全血基因组DNA,采用针对东亚人群的Illumina ASA芯片进行基因组扫描,根据基因组数据库定位相关基因。比较两组人群在相关基因位点上不同基因型的分布情况,采用logistic回归分析相关基因位点与ASCVD的关系。结果:通过Illumina ASA芯片检测到的与ASCVD可能有关的CYP21A2、ACVRL1、COL3A1、SCN5A、KCNA5、LDLR、PCSK9基因的突变位点中≥3例的位点包括:rs6467、rs202242769、rs121909285、rs587779580、rs1805124、rs121908591、rs13306515、rs11583680。其中CYP21A2基因的rs6467、PCSK9基因的rs11583680、SCN5A基因的rs1805124(均P<0.001),病例组与对照组人群的基因型分布差异有统计学意义。高血压亚组患者和对照组人群在rs6467和rs11583680位点上的基因型分布差异有统计学意义(P<0.001)。在校正混杂因素(年龄、性别、BMI、吸烟和体育锻炼)后,多因素logistic回归分析结果显示,与PCSK9基因位点rs11583680位点的CC基因型相比,C等位基因突变(CT+TT基因型)是ASCVD(OR=0.07,95%CI:0.008~0.68,P=0.02)及高血压(OR=0.045,95%CI:0.01~0.95,P=0.045)的保护性因素。结论:PCSK9基因的rs11583680位点与ASCVD有关。Objective:To explore the possible pathogenic mechanism of atherosclerotic cardiovascular disease(ASCVD)by comparing and analyzing the genetic polymorphisms between ASCVD high risk groups and healthy people.Methods:Patients who were treated in the Sichuan Provincial People’s Hospital from June 2019 to May 2020 were selected for the ASCVD overall risk assessment,and 203 patients with extremely high risk and high risk were included in the case group.Other 74 healthy subjects excluded from chronic cardiovascular and cerebrovascular diseases in the same period were selected into the control group.Genomic DNA was extracted from whole blood,and genome scanning was performed using Illumina ASA chip for East Asian populations,and relevant genes were located according to the genome database.The distribution of different genotypes at relevant gene loci was compared between the two groups,and the relationship between relevant gene loci and ASCVD was analyzed by logistic regression.Results:Among the mutation sites of CYP21 A2,ACVRL1,COL3 A1,SCN5 A,KCNA5,LDLR,and PCSK9 genes that may be related to ASCVD detected by the Illumina ASA chip,the sites with≥3 cases included rs6467,rs202242769,rs121909285,rs587779580,rs1805124,rs121908591,rs13306515,and rs11583680.The genotype distribution differences in rs6467 at CYP21 A2,rs11583680 at PCSK9,and rs1805124 at SCN5 A(all P<0.001)between the case group and the control group was statistically significant.The genotype distributions of rs6467 and rs11583680 between the hypertensive subgroup and the control group were statistically significant(P<0.001).After adjusting for confounding factors(age,sex,BMI,smoking,and physical exercise),multivariate logistic regression analysis showed that the C allele mutation(CT+TT genotype)was a protective factor for ASCVD(OR=0.07,95%CI:0.008-0.68,P=0.02)and hypertension(OR=0.045,95%CI:0.01-0.95,P=0.045)compared with CC genotype at rs11583680 of PCSK9 locus.Conclusion:rs11583680 at the PCSK9 gene may be associated with ASCVD.

关 键 词：动脉粥样硬化性心血管疾病 高血压 基因芯片 单核苷酸多态性 

分 类 号：R54[医药卫生—心血管疾病]