Oppert J M, Vohl M C, Chagnon M, Dionne F T, Cassard-Doulcier A M, Ricquier D, Pérusse L, Bouchard C
Physical Activity Sciences Laboratory, Laval University, Québec, Canada.
Int J Obes Relat Metab Disord. 1994 Aug;18(8):526-31.
The objective of this study was to identify DNA sequence variation in the UCP gene and to investigate its relationship with some obesity phenotypes. Two studies were carried out: (1) association study in unrelated subjects, and (2) sib-pair linkage analysis study in brothers and sisters. The subjects were 261 individuals from the Québec Family Study (123 parents and 138 offsprings from 64 families). The following were measured: Body mass index, percent body fat (measured by hydrostatic weighing), and subcutaneous fat (estimated by the sum of 6 skinfolds) were measured in 1978-81 and again 12 years later. Resting metabolic rate (RMR) was measured only in 1989-93. Genetic analyses were performed using Southern blotting technique and a human UCP genomic probe. (1) A BcII restriction fragment length polymorphism was identified with two alleles of 8.3 and 4.5 kb in length, and respective frequencies of 0.28 and 0.72. (2) In unrelated adults from the parental generation, a cross-sectional analysis of the 1989-93 data showed no difference in body fat and RMR between the UCP genotypes. No significant difference for the absolute changes in body fat over the 12-year period among the UCP genotypes was observed. However, a higher frequency (P < 0.05) of the 8.3-kb allele was found in high gainers compared to low gainers (i.e., above and below the median value) for percent body fat over the 12-year period. (3) No evidence of linkage between any of the obesity phenotypes and the UCP BcII marker was found. For the first time, the presence of DNA polymorphism in the human UCP gene is reported. Although, no significant association and linkage were found between the UCP BcII gene marker and body fat in the cohort of the Quebec Family Study, a higher frequency of the 8.3-kb allele was found in individuals who gained more body fat over time.
本研究的目的是鉴定解偶联蛋白（UCP）基因中的DNA序列变异，并研究其与某些肥胖表型的关系。进行了两项研究：（1）无关个体的关联研究；（2）兄弟姐妹间的同胞对连锁分析研究。研究对象为魁北克家庭研究中的261名个体（123名父母和来自64个家庭的138名后代）。测量了以下指标：1978 - 1981年以及12年后再次测量了体重指数、体脂百分比（通过水下称重法测量）和皮下脂肪（通过6个皮褶厚度之和估算）。静息代谢率（RMR）仅在1989 - 1993年进行了测量。使用Southern印迹技术和人UCP基因组探针进行了基因分析。（1）鉴定出一种BcII限制性片段长度多态性，有两个等位基因，长度分别为8.3 kb和4.5 kb，各自的频率为0.28和0.72。（2）在亲代的无关成年人中，对1989 - 1993年数据的横断面分析显示，UCP基因型之间的体脂和RMR没有差异。在UCP基因型中，未观察到12年期间体脂绝对变化的显著差异。然而，在12年期间体脂百分比增加较多者（即高于和低于中位数）中，发现8.3 kb等位基因的频率高于增加较少者（P < 0.05）。（3）未发现任何肥胖表型与UCP BcII标记之间存在连锁的证据。首次报道了人类UCP基因中存在DNA多态性。尽管在魁北克家庭研究队列中，未发现UCP BcII基因标记与体脂之间存在显著关联和连锁，但随着时间推移体脂增加更多的个体中，8.3 kb等位基因的频率更高。
