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  • Title: [Common variants in beta 3-adrenergic-receptor and uncoupling protein-2 genes are associated with type 2 diabetes and obesity].
    Author: Xiu LL, Weng JP, Sui Y, Wang J, Yan JH, Huang ZM.
    Journal: Zhonghua Yi Xue Za Zhi; 2004 Mar 02; 84(5):375-9. PubMed ID: 15061987.
    Abstract:
    OBJECTIVE: To investigate the effects of uncoupling protein-2 (UCP2) gene Ala55Val variation and beta(3)-adrenergic-receptor (beta(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 beta(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 beta(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 beta(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 mutations 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 beta(3)-AR gene Trp64Arg mutation is related with diabetes. The accumulation of the effects of two micro-genes creates obvious phenotypic effects.
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