|Hart Sailors, Mary|
Submitted to: Medicine and Science in Sports and Exercise
Publication Type: Abstract Only
Publication Acceptance Date: 3/19/2007
Publication Date: 5/7/2007
Citation: Hart Sailors, M.L., Jackson, A.S., Bray, M.S. 2007. The association of circadian clock candidate genes to increased adiposity in the TIGER study [abstract]. Medicine and Science in Sports and Exercise. 39(5 Suppl):S278. Interpretive Summary:
Technical Abstract: Obesity is a highly prevalent disease that has become a major health crisis in the United States. A number of studies have suggested a link between the altered sleep/wake patterns associated with our "24 hour" lifestyle and obesity. We hypothesize that disruption of the circadian clock intrinsic to the adipocyte, which may result from DNA sequence variation within clock-related genes, is a primary mechanism linking altered sleep/wake cycles to obesity. The purpose of this study was to investigate the association between body size and selected variants in clock-related genes (BMAL1, CLOCK, CRY, PER1, PER2, DBP, TEF, and E4BP4) in men and women (n=325) from the TIGER Study. We tested the association between single locus and multilocus genotypes and body-size measures (BMI, weight, waist and hip circumferences, skinfold percent fat, and DXA percent fat) using multivariate regression adjusted for age, gender, and smoking status. We found that variants in BMAL1 (rs2290034, rs3816358), TEF (rs2273071), and PER2 (rs934945) were significantly associated with body size measures in Hispanic males and females (n=74). The A alleles at each BMAL1 locus were associated with an increase in body size measures (rs2290034 AA/AG BMI = 30.5 kg/m**2, GG BMI = 26.2 kg/m2; rs3816358 AA/AG BMI = 31.2 kg/m**2, GG BMI = 27.6 kg/m2), while the G alleles in the TEF and PER2 variants were associated with increased body size measures (TEF GG/GA BMI = 28.9 kg/m2, AA BMI = 24.6 kg/m**2; PER2 GG/GA BMI = 28.8 kg/m**2, AA BMI = 23.5 kg/m**2). These genotype effects were consistent but non-significant in African Americans and non-Hispanic whites. We further investigated the joint effects of the TEF and PER2 variants with body size measures. Individuals with the homozygous GG genotype in both the TEF and PER2 polymorphisms were 4.8 times more likely to be obese (OR = 4.82, 95% CI (1.428-16.265)) compared to carriers of the A alleles in either TEF or PER2. A similar effect for the multilocus TEF/PER2 genotype was also observed for other body size measures, including BMI (p = 0.0016), waist circumference (p = 0.0096), and weight gain per year (p = 0.0391). These results suggest that variation within clock-related genes may be associated with body-size measures, thus potentiality linking increased adiposity to sleep/wake patterns.