关键词:解偶联蛋白2;胰岛素分泌;基因变异;2型糖尿病
【摘要】 目的 解偶联蛋白2(UCP2)基因定位于人类11q染色体区,该区域与高胰岛素血症及肥胖相关连。本研究拟探讨UCP2基因Ala55Val(A/V55)变异与中国人2型糖尿病患者胰岛素分泌/敏感性的关系。方法 359例无亲缘关系的中国人(据97年ADA标准分为:糖耐量正常者193例,2型糖尿病166例)及66例白种人用PCR-RFLP检测UCP2基因A/V55变异。结果 中国人(AA0.31,AV 0.51及VV 0.18)与白种人(AA 0.32,AV 0.56及VV 0.12)UCP2基因A/V55变异的基因型频率分布无显著差异(P=0.615),且该基因变异与中国人2型糖尿病发病无相关性(P=0.558)。在166例2型糖尿病患者中,UCP2基因A/V55变异与糖负荷3小时胰岛素总值(SUM)(P=0.0108),胰岛素曲线下面积(AUC)(P=0.0149)以及HOMAβ细胞功能(P=0.0174)相关。且糖负荷3小时C肽总值及C肽曲线下面积变化亦与胰岛素有相同趋势。结论 UCP2基因A/V55变异与中国人2型糖尿病患者葡萄糖兴奋后胰岛素分泌(GSIS)功能相关,提示该变异可能参与了中国人2型糖尿病胰岛素分泌不足的病理生理过程。
Association betweenAla55Val variant in the uncoupling protein 2 gene and glucose stimulated insulin secretionin type 2 diabetic Chinese
ZHENG Yiman,XIANG Kunsan,ZHANGRong,et al.
Department of Endocrinology andMetabolism,Shanghai Sixth People's Hospital,200233
【 Abstract 】 Objective To investigate the relationship between Ala55Val (A/V55)variant in the uncoupling protein 2 (UCP2) gene and insulin secretion/sensitivity in type2 diabetic Chinese. Methods By means of PCR-RFLP assay, the genotypes of A/V55 variantin the UCP2 gene were determined in 359 unrelated Chinese 〔 including 193 with normal glucose tolerance (NGT) and 166type 2 diabetics (DM) according to ADA 1997 criteria 〕 and 66 normal Caucasian subjects. Results No significantdifference (P=0.615) of genotype frequencies of the A/V55 variant in the UCP2 gene wasobserved between Chinese (AA 0.31, AV 0.51 and VV 0.18) and Caucasians (AA 0.32, AV 0.56and VV 0.12). There was also no difference in genotype frequencies between type 2diabetics and NGT group (P=0.558). All the observed genotype frequencies were inHardy-Weinberg equilibrium. Among the 166 type 2 diabetic Chinese, A/V55 variant in theUCP2 gene was correlated with the area under curve (AUC) of the insulin (P=0.0149) and thesum of the insulin values (P=0.0108) during oral glucose tolerance test (OGTT), as well aswith HOMA β cellfunction (P=0.0174). The changes of the AUC and the sum of C-peptide levels after 75gglucose challenge showed the same tendency. Conclusion A/V55 variant inthe UCP2 gene is correlated with the glucose stimulated insulin secretion from islet β cell in type 2 diabetic Chinese.It is suggested that A/V55 variant in the UCP2 gene may contribute to the dysfunction ofinsulin secretion in the pathogenesis of type 2 diabetes mellitus in Chinese.
【 Keywords 】 Uncouplingprotein 2 gene Insulinsecretion Genevariant Type 2diabetes mellitus
2型糖尿病是一种由遗传及环境因素共同作用引起的复杂病(complexdisease) ......
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