MTP基因多态性与2型糖尿病血管并发症的关系

Effect of microsomal triglyceride transfer protein(MTP) gene polymorphism on angiopathy in type 2 diabetes

目的探讨微粒体甘油三酯转移蛋白(MTP)基因多态性与2型糖尿病(T2DM)血管并发症的关系。方法采用PCRRFLP法和基因测序技术测定MTP493位点基因型,根据大血管并发症分组进行统计学分析。结果(1)MTP493位点存在G→T的单碱基变异。MTP基因型频率和T等位基因频率在T2DM有或无大血管并发症组间差异有统计学意义(χ2=9.162,P=0.01;χ2=10.322,P=0.001)。(2)与GG或GT组相比,TT组患者的TG、TC、VLDLC、LDLC水平均明显升高(P<0.05),HDLC明显降低(P=0.009)或有降低趋势。(3)Logistic多元逐步回归分析显示T等位基因、年龄、糖尿病病程、舒张压、TC是T2DM大血管病变的独立危险因素。HDLC与T2DM大血管病变发生呈负相关。结论携带MTP493TT基因型者易出现致动脉硬化性血脂异常,该基因型的糖尿病患者易出现大血管并发症。

Objective To investigate the relationship of MTP gene variation with type 2 diabetic angiopathy. Methods PCR and restriction-fragment-length polymorphism（PCR-RFLP） analysis and gene sequencing were used to investigate the influence of a common MTP gene polymorphism in promoter region on diabetic macroangiopathy. Results （1） A single nucleotide mutation of G→T was detected at 493 bp of upstream from the transcriptional start point. There was a significant difference in genotype frequency（χ^2 = 9. 162, P= 0. 01） and T allele frequency（χ^2 = 10. 322, P = 0. 001 ） between macroangiopathy group and non-macroangiopathy group. （2） MTP-493 TT group had the significantly higher serum levels of TC, TG, LDL-C, VLDL-C and lower HDL-C than other genotype groups. （3） Multivariate stepwise regression analysis showed that T allele, age, disease duration, diastolic blood pressure and total cholesterol were independent risk factors against type 2 diabetic macroangiopathy. The HDL-C level was negatively related with diabetic macroangiopathy. Conclusions MTP-493 TT genotype may be deeply involved in production of atherogenic dyslipidemia and associated with development of macroangiopathy in type 2 diabetic subjects.