解偶联蛋白2基因Ala55V al变异与中国人2型糖尿病患者葡萄糖兴奋后胰岛素分泌功能的关系

Association between Ala55Val variant in the uncoupling protein 2 gene and glucose stimulated insulin secretion in type 2 diabetic Chinese

目的 解偶联蛋白２（ Ｕ Ｃ Ｐ２） 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 Ｕ Ｃ Ｐ２ 基因 Ａｌａ５５ Ｖａｌ（ 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 Ａ Ｄ Ａ 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 Ｐ Ｃ Ｒ Ｒ Ｆ Ｌ Ｐ 检测 Ｕ Ｃ Ｐ２ 基因 Ａ／ Ｖ５５ 变异。结果 中国人（ Ａ Ａ０ ．３１ ， Ａ Ｖ０ ．５１ 及 Ｖ Ｖ０ ．１８） 与白种人（ Ａ Ａ０ ．３２ ， Ａ Ｖ０ ．５６ 及 Ｖ Ｖ０ ．１２） Ｕ Ｃ Ｐ２ 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， Ｕ Ｃ Ｐ２ 基因 Ａ／ Ｖ５５ 变异与 糖负荷３ 小时 胰岛素总值（ Ｓ Ｕ Ｍ）（ Ｐ＝０ ．０１０８） ，胰岛素曲线下面积（ Ａ Ｕ Ｃ）（ Ｐ＝ ０ ．０１４９） 以及 Ｈ Ｏ Ｍ Ａβ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 Ｕ Ｃ

Objective To investigate the relationship between Ala55Val (A/V55) variant in the uncoupling protein 2 (UCP2) gene and insulin secretion/sensitivity in type 2 diabetic Chinese. Methods By means of PCR RFLP assay, the genotypes of A/V55 variant in the UCP2 gene were determined in 359 unrelated Chinese 〔including 193 with normal glucose tolerance (NGT) and 166 type 2 diabetics (DM) according to ADA 1997 criteria〕 and 66 normal Caucasian subjects. Results No significant difference (P=0.615) of genotype frequencies of the A/V55 variant in the UCP2 gene was observed between Chinese (AA 0.31, AV 0.51 and VV 0.18) and Caucasians (AA 0.32, AV 0.56 and VV 0.12). There was also no difference in genotype frequencies between type 2 diabetics and NGT group (P=0.558). All the observed genotype frequencies were in Hardy Weinberg equilibrium. Among the 166 type 2 diabetic Chinese, A/V55 variant in the UCP2 gene was correlated with the area under curve (AUC) of the insulin (P=0.0149) and the sum of the insulin values (P=0.0108) during oral glucose tolerance test (OGTT), as well as with HOMA β cell function (P=0.0174). The changes of the AUC and the sum of C peptide levels after 75g glucose challenge showed the same tendency. Conclusion A/V55 variant in the 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 of insulin secretion in the pathogenesis of type 2 diabetes mellitus in Chinese.