[Common variants in beta 3-adrenergic-receptor and uncoupling protein-2 genes are associated with type 2 diabetes and obesity].
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).


CONCLUSIONS
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.
Xiu
Ling-ling
LL
Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Weng
Jian-ping
JP
Sui
Yi
Y
Wang
Jing
J
Yan
Jin-hua
JH
Huang
Zhi-min
ZM
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics*; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D022702:Receptors, Adrenergic, beta-3; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2