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

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

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。

Objective To understand the role of insulin - receptor（INSR） gene Exon17 in the development of insulin resistance（IR） on a populationbased 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 nueleotide 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 frequen- cies 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.