Valve R, Heikkinen S, Rissanen A, Laakso M, Uusitupa M
Department of Clinical Nutrition, University of Kuopio, Finland.
Diabetologia. 1998 Mar;41(3):357-61. doi: 10.1007/s001250050915.
The polymorphisms in the uncoupling protein 1 (UCP1, A to G) and beta3-adrenergic receptor (beta3-AR, Trp64Arg) genes have been suggested to be associated with an increased tendency to gain weight. We investigated the frequency of the A to G polymorphism of the UCP1 gene and its effect on basal metabolic rate (BMR) among obese Finns. We also examined the effects of the simultaneous occurrence of the polymorphisms in the UCP1 and beta3-AR genes on BMR. Altogether 170 obese subjects (29 men, 141 women, BMI 34.7beta3.8 kg/m2, age 43+/-8 years, mean+/-SD) participated in the study. The A to G substitution of the UCP1 gene was verified by digestion of the PCR product with Bcl I. The frequency of the A to G polymorphism of the UCP1 gene in obese subjects did not differ significantly from the population-based control subjects (5 vs 1 % for homozygotes (GG) and 35 vs 42 % for heterozygotes (AG), p=0.077, for trend). BMR adjusted for lean body mass, age and sex (adjBMR) was similar among the three UCP1 gene genotypes of obese subjects (AA n=90, AG n=72 or GG n=8). However, the subjects with the polymorphisms in both UCP1 and beta3-AR genes (n=18) had a 79 kcal/day (95% CI 30-128) lower adjBMR than the subjects without these polymorphisms (n=76) (1551+/-77 vs 1629+/-141 kcal/day, p=0.002). Furthermore, adjBMR was 63 kcal/day (95 % CI 7-118 kcal/day) lower in the subjects with both polymorphisms (n=18) compared with the subjects (n=14) who had only the polymorphism in the beta3-AR gene (1551+/-77 vs 1613+/-76 kcal/day, p=0.028). The A to G polymorphism of the UCP1 gene did not have an independent effect on BMR, but its simultaneous existence with the Trp64Arg polymorphism of the beta3-AR gene resulted in more lowered BMR than the Trp64Arg polymorphism of beta3-AR gene alone.
解偶联蛋白1（UCP1，A到G）基因和β3 - 肾上腺素能受体（β3 - AR，色氨酸64精氨酸）基因的多态性被认为与体重增加倾向增强有关。我们研究了UCP1基因A到G多态性的频率及其对肥胖芬兰人基础代谢率（BMR）的影响。我们还研究了UCP1和β3 - AR基因多态性同时存在对BMR的影响。共有170名肥胖受试者（29名男性，141名女性，BMI 34.7±3.8kg/m²，年龄43±8岁，均值±标准差）参与了该研究。通过用Bcl I消化PCR产物来验证UCP1基因的A到G替换。肥胖受试者中UCP1基因A到G多态性的频率与基于人群的对照受试者相比无显著差异（纯合子（GG）分别为5%对1%，杂合子（AG）分别为35%对42%，趋势p = 0.077）。肥胖受试者的三种UCP1基因基因型中，经去脂体重、年龄和性别校正后的BMR（adjBMR）相似（AA型n = 90，AG型n = 72，GG型n = 8）。然而，UCP1和β3 - AR基因均有多态性的受试者（n = 18）的adjBMR比没有这些多态性的受试者（n = 76）低79千卡/天（95%可信区间30 - 128）（分别为1551±77千卡/天和1629±141千卡/天，p = 0.002）。此外，与仅β3 - AR基因有多态性的受试者（n = 14）相比，两种多态性均有的受试者（n = 18）的adjBMR低63千卡/天（95%可信区间7 - 118千卡/天）（分别为1551±77千卡/天和1613±76千卡/天，p = 0.028）。UCP1基因的A到G多态性对BMR没有独立影响，但它与β3 - AR基因的色氨酸64精氨酸多态性同时存在时，导致的BMR降低比单独的β3 - AR基因色氨酸64精氨酸多态性更明显。
