ADAMTS7基因rs922693位点多态性与大动脉粥样硬化型脑梗死的相关性  

Association between ADAMTS7 gene rs922693polymorphism and atherosclerotic cerebral infarction

作　　者：陈林发 袁燕泉 李友 黄志勇[1] 颜津津[1] CHEN Lin-fa;YUAN Yan-quan;LI You;HUANG Zhi-yong;YAN Jin-jin(Department of Neurology,Huizhou Third People's Hospital,Guangzhou Medical University Huizhou Hospital,Huizhou,Guangdong 516002,China;Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases,Affiliated Hospital of Guangdong Medical University,Zhanjiang,Guangdong 524001,China)

机构地区：[1]广州医科大学惠州医院惠州市第三人民医院神经内科,广东惠州516002 [2]广东医科大学附属医院神经病学研究所广东省衰老相关心脑疾病重点实验室,广东湛江524001

出　　处：《中华实用诊断与治疗杂志》2022年第10期981-984,共4页Journal of Chinese Practical Diagnosis and Therapy

基　　金：国家自然科学基金(81571157);惠州市科技计划(医疗卫生)项目(2021WC0106153)。

摘　　要：目的探讨含Ⅰ型血小板结合蛋白基序的去整合素金属蛋白酶7(a disintegrin and metalloproteinase with thrombospondin motifs 7,ADAMTS7)基因rs922693位点多态性与大动脉粥样硬化型脑梗死(large artery atherosclerotic cerebral infarction,LAACI)易感性的关系。方法LAACI患者689例为LAACI组,体检健康者712例为对照组,2组均采用SNaPshot小测序技术进行基因分型,比较2组基因型和等位基因频率。采用多因素logistic回归分析LAACI发生的风险基因。随机选取LAACI组65例和对照组68例,采用实时荧光定量PCR法检测外周血单个核细胞ADAMTS7mRNA相对表达量,并进行比较。结果LAACI组ADAMTS7基因rs922693位点等位基因A频率(53.1%)、基因型AA频率(26.9%)、隐性模型比率(79.4%)均高于对照组(48.0%、22.1%、73.9%)(P<0.05),显性模型比率(73.1%)低于对照组(77.9%)(χ2=4.369,P=0.040)。ADAMTS7基因rs922693位点等位基因A携带者LAACI发生风险是等位基因G的1.23倍(95%CI:1.06~1.43,P=0.026),基因型AA携带者LAACI发生风险是基因型GG的1.54倍(95%CI:1.14~2.09,P=0.005),显性模型含G等位基因型(GG+GA)携带者LAACI发生风险是基因型AA的0.77倍(95%CI:0.60~0.98,P=0.040),隐性模型含A等位基因型(GA+AA)携带者LAACI发生风险是基因型GG的1.36倍(95%CI:1.06~1.75,P=0.032)。LAACI组外周血单个核细胞ADAMTS7mRNA相对表达量(0.85±0.13)高于对照组(0.64±0.09)(t=-10.872,P<0.001);LAACI组ADAMTS7基因rs922693位点基因型GA+AA携带者外周血单个核细胞ADAMTS7mRNA相对表达量(0.92±0.06)高于基因型GG携带者(0.75±0.07)(t=-9.260,P<0.001)。结论ADAMTS7基因rs922693位点多态性与LAACI易感性相关,rs922693位点等位基因A和基因型AA是LAACI发生的风险因素,rs922693位点等位基因A可能通过上调ADAMTS7基因表达参与LAACI发生。Objective To investigate the association between a disintegrin and metalloproteinase with thrombospondin motifs 7(ADAMTS7)polymorphisms and the susceptibility to atherosclerotic cerebral infarction(LAACI).Methods Multiplex SNaPshot was used for genotyping rs922693polymorphism in 689LAACI patients(LAACI group)and 712 healthy volunteers(control group).The allele and genotype frequencies were compared between two groups.Multivariate logistic regression analysis was done to assess the risk gene of LAACI.Sixty-five patients from LAACI group and 68 patients from control group were randomly selected,and the relative expression of ADAMTS7mRNA in peripheral blood mononuclear cells was detected by real-time fluorescence quantitative PCR and was compared between two groups.Results The ADAMTS7 gene rs922693Aallele frequency,AA genotype frequency and recessive model ratio were higher in LAACI group(53.1%,26.9%,79.4%)than those in control group(48.0%,22.1%,73.9%)(P<0.05),and the dominant model ratio was lower in LAACI group(73.1%)than that in control group(77.9%)(χ2=4.369,P=0.040).The risk of LAACI was 1.23times higher in ADAMTS7 rs922693Aallele carriers than in G allele carriers(95%CI:1.06-1.43,P=0.026),was 1.54times higher in AA genotype carriers than in GG genotype carriers(95%CI:1.14-2.09,P=0.005),was 0.77times in G allele carriers of dominant model(GG+GA)than in AA genotype carriers(95%CI:0.60-0.98,P=0.040),and was 1.36times higher in A allele carriers of recessive model(GA+AA)than in GG genotype carriers(95%CI:1.06-1.75,P=0.032).The relative expression of ADAMTS7mRNA was significantly higher in LAACI group(0.85±0.13)than that in control group(0.64±0.09)(t=-10.872,P<0.001),and was higher in rs922693GA+AA genotype carriers(0.92±0.06)than that in GG genotype carriers(0.75±0.07)(t=-9.260,P<0.001).Conclusions ADAMTS7 rs922693gene polymorphism is associated with the susceptibility to LAACI,and rs922693 AA genotype and A allele are the risk factors of LAACI.A allele may participate in the pathogenesis of LAACI by upregulat

关 键 词：大动脉粥样硬化型脑梗死 含Ⅰ型血小板结合蛋白基序的去整合素金属蛋白酶7 rs922693位点 基因多态性 

分 类 号：R743.3[医药卫生—神经病学与精神病学]