某特定人群胰岛素受体基因EXON17多态性与胰岛素抵抗的发生

目的从群体角度探讨胰岛素受体(INSR)基因第17外显子(Exon17)变异与胰岛素抵抗(IR)的发生。方法采用聚合酶链反应(PCR)对某一特定队列中国人群(345名)的INSR基因Exon17进行扩增,并用PCR产物直接测序法进行单核苷酸序列分析。结果(1)男性发生胰岛素抵抗(IR)的风险是女性的1.83倍(P<0.05)。(2)在Exon17测得3个单核苷酸多态(SNPs),即10798位点的G缺失(1017位天门冬氨酸),10954位点的C→CA(1069位亮氨酸),10961位点的T→TA(1071位苯丙氨酸)。生化指标分析发现,10798位点G缺失者的甘油三脂水平低于不缺失者(P>0.05),缺失者的高密度脂蛋白水平高于不缺失者(P<0.05)。按性别分层,3个SNPs的等位基因频率在IR组和对照组的分布差异均不显著。结论INSR基因Exon17的3个SNPs改变可能并不直接参与IR的发生。

ROLE OF POLYMORPHISM OF EXON17 OF INSULIN-RECEPTOR GENE IN THE DEVELOPMENT OF INSULIN RESISTANCE IN CERTAIN SPECIAL POPULATION

Objective To understand the role of insulin-receptor(INSR) gene Exon17 in the development of insulin resistance(IR) on a population-based study in China.Methods Polymerase chain reaction(PCR) was used to amplify the Exon17 of INSR gene and all amplified products were analyzed by direct sequencing.Results(1) Among the 345 cases,HDL cholesterol was higher in males than in females (P<0.05).The proportion of IR in males(64.4%) was higher than that in females(35.6%,OR=1.83,P<0.05).(2)Three single nucleotide polymorphisms(SNPs) were found at the following loci: deletion of G at 10798(Asp1017),C to CA at 10954(Leu1069),T to TA at 10961(Phe1071).The data were in agreement with the test of Hardy-Weinberg balance(P>0.05).The biochemical indices in different loci in Exon17 showed that the individuals who had deletion G at 10798 locus had lower TG(P>0.05) but higher HDL(P<0.05) than those without deletion G on the same site.After sex stratifying analysis,all allele frequencies on the three loci of SNPs of Exon17 had different distributions between the IR group and the control group,but(P>0.05).Conclusion Three SNPs of Exon17 of INSR gene are unlikely to play a direct role in the pathogenesis of human disorders with IR.