GAS6基因多态性及血浆水平与昆明地区汉族2型糖尿病合并动脉粥样硬化的相关性

S6 gene polymorphism and plasma level with type 2 diabetes mellitus complicated with atherosclerosis in Kunming Han population

目的探讨生长停滞特异性蛋白6(GAS6)基因多态性及血浆水平与昆明地区汉族2型糖尿病合并动脉粥样硬化(T2DM-AS)的相关性。方法收集181例单纯T2DM患者、171例T2DM-AS患者和186例正常对照(NC)者,运用PCR和单向基因测序检测GAS6基因多态性,ELISA检测血浆GAS6水平,并分析其基因型及等位基因频率、血浆GAS6水平和相关临床指标。结果T2DM组分别与NC组、T2DM-AS组相比,三种基因型频率的分布无差异(χ^2=8.031,P=0.018;χ^2=1.762,P=0.414);T2DM-AS组GG基因型频率高于NC组,GA、AA基因型频率低于NC组,差异有统计学意义(χ^2=9.286,P=0.010)。T2DM组和T2DM-AS组的A等位基因频率低于NC组,G等位基因频率高于NC组,差异有统计学意义(χ^2=7.493,P=0.006;χ^2=8.718,P=0.003);T2DM-AS组和T2DM组相比,等位基因频率的分布无差异(χ^2=0.069,P=0.793)。T2DM组和T2DM-AS组的体重指数(BMI)、收缩压(SBP)、舒张压(DBP)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FBG)均高于NC组(P<0.01),而高密度脂蛋白胆固醇(HDL-C)和GAS6水平低于NC组(P<0.01);T2DM-AS组的病程、SBP和血管内中膜厚度(IMT)均高于T2DM组,差异有统计学意义(P<0.01),而GAS6水平与T2DM组相比无差异(P>0.05)。T2DM病程、饮酒、SBP是AS发生的危险因素(OR:1.072、2.625、1.019;95%CI:1.024-1.122、1.241-5.552、1.003-1.035)。HDL-C是AS的保护性因素(OR=0.253;95%CI:0.071-0.902);而GAS6基因rs8191974多态性及其血浆水平可能与AS无关联。结论本研究尚未发现GAS6基因rs8191974多态性及其血浆水平与昆明地区汉族AS之间的关联。T2DM病程、饮酒、高血压是AS发生的危险因素,HDL-C是AS的保护性因素。

Objective The aim of this study was to investigate the association of growth arrest specific protein 6(GAS6)gene polymorphism and plasma level with type 2 diabetes mellitus complicated with atherosclerosis(T2 DM-AS)in Kunming Han population.Methods Peripheral venous blood was collected from 181 patients with type 2 diabetes,171 patients with T2 DM-AS and 186 normal controls.Rs8191974 polymorphism was detected by PCR and unidirectional gene sequencing.The plasma GAS6 level was detected by ELISA,and the genotype frequency,allele frequency,plasma GAS6 level and related clinical indexes were analyzed.Results There was no difference in the frequency distribution of the three genotypes between T2 DM group and NC group,T2 DM-AS(χ^2=8.031,P=0.018;χ^2=1.762,P=0.414).The frequency of GG genotypes in the T2 DM-AS group was higher than that in the NC group,but the frequency of GA and AA genotype was lower(χ^2=9.286,P=0.010).(2)Compared with NC group,the frequency of allele A was lower,but allele G was higher in T2 DM and T2 DM-AS groups(χ^2=7.493,P=0.006;χ^2=8.718,P=0.003).There was no difference in allele frequency between T2 DM-AS and T2 DM group(χ^2=0.069,P=0.793).Compared with NC group,the levels of Body Mass Index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),total cholesterol(TC),triglycerides(TG),low density lipoprotein cholesterol(LDL-C)and fasting plasma glucose(FBG)were higher(P<0.01),but the levels of high-density lipoprotein cholesterol(HDL-C)and GAS6 were lower in T2 DM and T2 DM-AS group(P<0.01).Compared with T2 DM group,the course of T2 DM,SBP and intima media thickness(IMT)were higher in T2 DM-AS group(P<0.01),but there was no difference in GAS6 level between T2 DM and T2 DM-AS group(P>0.05).The course of T2 DM,alcohol consumption and SBP are the risk factors of AS(OR:1.072,2.625,1.019;95%CI:1.024-1.122,1.241-5.552,1.003-1.035).HDL-C is a protective factor for AS(OR:0.253;95%CI:0.071-0.902.However,GAS6 gene rs8191974 polymorphism and plasma level may not be associated with AS.Conclusion The association of GAS6 gene rs8191974 polymorphism and plasma level with AS has not been found in Kunming Han population.The course of T2 DM,alcohol consumption and hypertension are risk factors for AS.HDL-C is a protective factor for AS.