SPARCL1基因多态性与动脉粥样硬化遗传易感相关性分析  

Correlation between SPARCL1 gene polymorphism and genetic susceptibility to atherosclerosis

作　　者：陈心严 程煦 陈婷婷[3] 王华[4,5] 张敏[1] 朱华庆[6] 程筱雯[1] Chen Xinyan;Cheng Xu;Chen Tingting;Wang Hua;Zhang Min;Zhu Huaqing;Cheng Xiaowen(Dept of Clinical Laboratory,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;Dept of Cardiovascular Surgery,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;Dept of Pathology,Anhui Medical University,Hefei 230032;Dept of Oncology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;Key Laboratory of Anto-inflammatory and Immune Medicines,Anhui Medical University,Hefei 230032;Laboratory of Molecular Biology and Dept of Biochemistry,Anhui Medical University,Hefei 230032)

机构地区：[1]安徽医科大学第一附属医院检验科,合肥230022 [2]安徽医科大学第一附属医院心脏外科,合肥230022 [3]安徽医科大学病理教研室,合肥230032 [4]安徽医科大学第一附属医院肿瘤科,合肥230022 [5]安徽医科大学炎症免疫性疾病安徽省实验室,合肥230032 [6]安徽医科大学生化与分子生物学教研室,合肥230032

出　　处：《安徽医科大学学报》2023年第5期872-875,884,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:82170484)。

摘　　要：目的探讨富含半胱氨酸的酸性分泌蛋白类似蛋白1(SPARCL1)的单核苷酸多态性(SNP)位点rs7695558、rs1049539与动脉粥样硬化(AS)的遗传易感相关性。方法采用病例对照研究,选取209例AS患者作为病例组,年龄、性别相匹配的208例健康体检者作为对照组。利用酶联免疫吸附试验(ELISA)测定血清SPARCL1表达水平,使用线性和Logistic回归分析评估SPARCL1水平和血管危险因素、生活方式、人口统计学变量之间的相关性。通过免疫组织化学实验评估发生粥样硬化病变的动脉组织和相对正常动脉组织中的SPARCL1蛋白的表达水平及定位,随后用高分辨率熔解曲线法对51例AS患者和50例健康对照者DNA的SPARCL1基因的两个SNP位点rs7695558(A/G)、rs1049539(T/C)进行基因分型,使用Pearsonχ2检验分别分析rs7695558、rs1049539多态性与AS患者易感性之间的关系。结果AS患者的SPARCL1血清表达水平低于对照组(Z=-2.916,P=0.004)。SPARCL1水平与患者年龄(P=0.027)、舒张压(P=0.008)有关,而与患者的性别及部分心血管危险因素无明显相关(P>0.05)。冠状动脉组织中粥样硬化病变部位的SPARCL1表达水平增高。rs7695558和rs1049539在病例组和对照组间的基因分布差异无统计学意义(P>0.05)。rs7695558的隐性遗传模型中,含A和不含A的基因分布有差异,不含A等位基因(GG)的患者比含A等位基因(AA+AG)的患者的AS发病风险低,OR值为0.417,95%CI:0.184~0.945,在10%的置信水平上显著(P=0.034)。结论首次在中国安徽人群中鉴定了位于人类SPARCL1基因内含子内的与AS风险相关的新易感位点rs7695558,同时提示SPARCL1可能作为血管保护因子发挥抗AS作用。Objective To investigate the expression of secreted protein acidic and rich in cysteine-like 1(SPARCL1)in atherosclerosis(AS)and the association between SPARCL1 gene rs7695558 and rs1049539 polymorphism with the susceptibility to AS.Methods In this case-control study,209 AS patients were selected as the case group,and 208 healthy matched in age and sex were selected as the control group.The expression level of serum SPARCL1 was measured by enzyme-linked immunosorbent assay(ELISA).Linear and Logistic regression analysis were used to evaluate the correlation between SPARCL1 level and vascular risk factors,lifestyle and demographic variables.Expression of SPARCL1 in tissue specimens was assessed by immunohistochemistry.Single nucleotide polymorphisms(SNPs)were genotyped by high resolution melting method.Chi-square test was used to analyze the relationship between rs7695558 and rs1049539 polymorphism and susceptibility to AS.Results The serum expression level of SPARCL1 in AS patients was lower than that in healthy controls(Z=-2.916,P=0.004).The level of SPARCL1 was related to age(P=0.027)and diastolic blood pressure(P=0.008),but not to sex and other cardiovascular risk factors(P>0.05).The expression level of SPARCL1 in atherosclerotic lesions of coronary artery tissue increased.There was no significant difference in gene distribution of rs7695558 and rs1049539 between the case group and the control group by chi-square test(P>0.05).In the recessive genetic model of rs7695558,there was a difference in the distribution of genes with and without A.Patients without A allele(GG)had a lower risk of AS than patients with A allele(AA+AG).The OR value was 0.417,95%CI:0.184~0.945,which was significant at 10%confidence level(P=0.034).Conclusion Rs7695558,a new susceptible site related to AS risk,located in the intron of human SPARCL1 gene is identified for the first time in Anhui population of China,suggesting that SPARCL1 may play an anti-AS role as a vascular protective factor.

关 键 词：动脉粥样硬化 SPARCL1 基因多态性 遗传易感性 

分 类 号：R543.5[医药卫生—心血管疾病]