摘要
目的 研究解偶联蛋白 2 (UCP2 )基因Ala5 5Val变异和 β3 肾上腺素能受体 (β3 AR)基因Trp6 4Arg变异对 2型糖尿病和肥胖症的影响 ,以及两基因变异是否起协同的作用。方法 用聚合酶链反应 限制性片段长度多态性方法 ,对 177名正常对照、173例 2型糖尿病病人和 119例肥胖症病人进行UCP2基因Ala5 5Val变异和 β3 AR基因Trp6 4Arg变异的检测。比较分析在不同组间基因型频率、基因型组合、临床变量等的分布差异。联合分析UCP2基因变异和 β3 AR基因变异在 2型糖尿病和肥胖症的发病中有无协同效应。结果 ① 2型糖尿病和肥胖症组中UCP2基因Ala5 5Val纯合子变异的基因频率明显高于正常对照组 (分别为 2 3 7%、2 1 8%、7 9% ,OR =4 6 2 ,P =0 0 0 1;OR =3 71,P =0 0 0 1) ;正常人携带Ala5 5Val基因变异者体重指数 (kg/m2 ) (2 2 2± 1 8)高于非携带者(2 1 6± 2 1)。② 2型糖尿病组 β3 AR基因Trp6 4Arg纯合子变异的基因频率 (5 2 % )明显高于正常组(40 % ) ;正常人携带Trp6 4Arg基因变异者有较高的空腹和口服葡萄糖耐量试验后 2h血糖水平。③当单一的UCP2或 β3 AR基因变异时 ,在 2型糖尿病组及肥胖组均与正常人的分布差别无显著意义(P >0 0 5 ) ;当UCP2和 β3 AR两基因同时发生变异时 ,2型糖?
Objective To investigate the effects of uncoupling protein-2 (UCP2) gene Ala55Val variation and β 3- adrenergic-receptor (β 3-AR) gene Trp64Arg variation on type 2 diabetes and obesity, as well as the combined effects between the two variations. Methods The peripheral blood samples of 173 type 2 diabetics, 119 obese persons, and 177 control subjects were collected. PCR-RFLP was used to detect the UCP2 gene Ala55Val variation and β 3-AR gene Trp64Arg variation. The haplotype and allele frequency distributions among the three groups were analyzed. The combined effect of the two gene mutations was analyzed too. Results (1) The frequencies of homozygote of UCP2 gene Ala55Val variation in the diabetes and obesity patients were both significantly higher than that in the control subjects (OR=4.62, P=0.001;OR=3.71, P=0.001). The Ala55Val variation carriers had higher BMI in the control subjects. (2)The gene frequency of homozygote of β 3-AR gene Trp64Arg variation was significantly higher in the diabetes patients than in the control subjects. The Trp64Arg variation carriers had higher fasting and 2-hour postgrandual glucose levels than the non-carriers in the control subjects. (3) When there was only UCP2 gene mutation or β 3-AR gene mutation, their frequencies in diabetes and obesity patients were not significantly different from that in the control subjects (both P>0.05). However, the frequencies of the combined mutatations of these two genes in either the diabetes patients or in the obesity patients were both significantly higher than in the control subjects (OR=3.69, P=0.000; OR=2.57, P=0.009). (4) The Val/Val+ Trp/Arg carriers had the greatest relation with diabetes (OR=10.43, P=0.000) and obesity (OR=8.58, P=0.002). Conclusion The homozygote of UCP2 gene Ala55Val mutation significantly enhances the risks of diabetes and obesity. The homozygote of β 3-AR gene Trp64Arg mutation is related with diabetes. The accumalation of the effects of two micro-genes creates obvious phenotypic effects.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2004年第5期375-379,共5页
National Medical Journal of China
基金
广东省科技攻关资助项目 (B3 0 2 0 1)
