Contribution of several candidate gene polymorphisms in the determination of adiposity changes:: results from the Quebec Family Study

Background: Several candidate genes have been associated with obesity, but very few studies have tested more than one gene simultaneously. Methods: In this study, 15 polymorphisms in 10 candidate genes of obesity were tested for association with changes in adiposity measured over a period of 6-10 years in a maximum of 332 adult subjects with a wide range of adiposity (17.5 < body mass index (BMI) < 55.6 kg/m(2)) from the Quebec Family Study. Stepwise regression models were used to identify the combination of genes explaining changes in adiposity after adjustment for age (initial value), gender, initial value of the adiposity variable and duration of follow-up. Analyses were carried out in the whole sample and repeated while stratifying on age (< 40 and >= 40 years). Results: In the whole sample, the variance in age- related adiposity changes explained by the candidate gene polymorphisms ranged from 3.1% (BMI, P < 0.05) to 8.5% (fat mass (FM), P <= 0.0005). The genes retained in the prediction model for changes in FM were leptin (P <= 0.05), guanine nucleotide binding protein beta 3 (P <= 0.05), adrenergic receptor beta 3 (P <= 0.05), neuromedin beta (P <= 0.05) and peroxisome proliferator-activated receptor-gamma 2 (P <= 0.10). The effects of the genes were significant in both age groups, but the genes contributing to adiposity changes were different and their effects were stronger in the younger than in the older age group. Conclusion: This study suggests that models including genetic information from several candidate gene polymorphisms can significantly contribute to the changes in adiposity over time, that different genes may act at different ages and that genetic information could be useful for the identification of individuals at high risk for gaining body fat over time.