Stydy of relationship of sulfonylurea receptor-1 gene polymorphism with high insulin secretion levels in non-diabetes Chinese

目的 了解磺脲类药物受体(SUR)基因多态性与中国汉族人糖尿病高危人群血清胰岛素浓度的关系。方法采用多聚酶链式反应-限制性酶切片段长度多态性分析技术(PCR-RFLP)对SUR基因第24内含子的多态性进行分析，采用放射免疫法(RIA)测定血清胰岛素浓度。结果 SUR基因第24内含子的“c”等位基因频率在206例有2型糖尿病家族史而彼此间无血缘关系的糖耐量试验正常人(A组)中较110例正常对照者(B组)显著升高(64% vs 54%，P=0.004)，且“cc”纯合子基因型的频率亦在此人群中显著升高(38% vs 24%，P=0.002)。A组人群中纯合子“cc”基因型者BMI(27.27±6.37 vs 24.99±3.43kg/m2，P＜0.05；27.27±6.37 vs 25.28±2.78kg/m2，P＜0.05)、空腹及口服75g葡萄糖后2小时血清胰岛素(15.52±10.72 vs 9.27±5.03U/ml,P＜0.01；15.52±10.72 vs 10.79±7.80U/ml,P＜0.05及76.41±54.02 vs 55.43±49.60U/ml,P＜0.01；76.41±54.02 vs 55.71±40.39,P＜0.05)、HOMA(Ri) (4.00±3.09 vs 2.79±1.32,P＜0.01；4.00±3.09 vs 2.82±2.94,P＜0.01)及ISI(-4.22±0.75 vs -3.69±0.57，P＜0.01；-4.22±0.75 vs -3.75±0.94,P＜0.01)均显著高于其它基因型者。结论 本研究表明SUR基因的缺陷可能导致胰岛素的高分泌，而后者可能是后继的体重增加及胰岛素敏感性降低的原因之一。本研究结果支持在糖尿病发病的自然病程中高胰岛素分泌为初始病因的假说。Objective A recent study has shown the association between a sulfonylurea receptor gene 1 (SUR1) variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group,supporting the hypothesis that the primary insulin hypersecretion may be an antecedent of type 2 diabetes.Methods To test this hypothesis in Chinese population,we studied the allele and genotype distribution of the polymorphism at -3 position of intron 24 in SUR1 by PCR RFLP technique in 206 unrelated normal glucose tolerant subjects with strong family history of type 2 diabetes (group A) and 110 normal individuals without family history of diabetes (group B).Results The frequency of “-3c” allele and “-3cc” genotype of intron 24 in group A was significantly higher than that in group B (64% vs 54%, P =0 004 and 38% vs 24%, P =0.002 respectively).Moreover,in group A, those carrying “cc” genetype had a higher BMI (27 27±6 37 vs 24.99±3.43kg/m 2, P <0.05;27 27±6 37 vs 25.28±2.78kg/m 2, P <0.05),fasting insulin (15 52±10 72 vs 9.27±5.03U/ml, P <0.01;15 52±10 72 vs 10.79±7.80U/ml, P <0.05) and 2h insulin levels (76.41±54 02 vs 55.43±49.60U/ml, P <0.01;76 41±54 02 vs 55.71±40.39, P <0.05) as well as lower insulin sensitivity [HOMA(R i]: 4.00±3.09 vs 2.79±1.32, P <0.01; 4.00±3.09 vs 2.82±2.94, P <0.01) as compared with that in carriers of other genotypes (“ct” and “tt”).Conclusion This study suggested the possibility that the defect in SUR1 gene might contribute to the insulin hypersecretion which might be the cause of subsequent increased body weight and decreased insulin sensitivity.中国科学引文数据库(CSCD)014-7