|Hart Sailors, M. - BAYLOR COLLEGE MED|
|Folsom, A. - UNIV. OF MINNESOTA|
|Ballantyne, C. - BAYLOR COLLEGE MED|
|Hoelscher, D. - UT HEALTH SCIENCE CENTER|
|Jackson, A. - UNIV. OF HOUSTON|
|Linda Kao, W. - JOHN HOPKINS SCHOOL OF PU|
|Pankow, J. - UNIV. OF MINNESOTA|
Submitted to: Diabetes Obesity and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 8, 2006
Publication Date: September 2, 2007
Citation: Hart Sailors, M.L., Folsom, A.R., Ballantyne, C.M., Hoelscher, D.M., Jackson, A.S., Linda Kao, W.H., Pankow, J.S., Bray, M.S. 2007. Genetic variations and decreased risk for obesity in the Atherosclerosis Risk in Communities Study. Diabetes, Obesity and Metabolism. 9(4):548-557. Interpretive Summary: Variation in DNA sequence can influence the risk of developing disease by altering the genes and proteins encoded by the sequence. The purpose of this study was to investigate the effects of DNA sequence variation in the leptin (LEP) and melanocortin-4 receptor (MC4R) genes on obesity-related traits in 13,405 African-American (AA) and white participants from the Atherosclerosis Risk in Communities (ARIC) Study. We found that AA females who had the less common forms of both of these genes were 63% less likely to be obese, and white females with the same two forms of the gene were 46% less likely to be obese compared to those individuals with the more common forms of the two genes. This study indicates that genes can interact to influence the development of obesity in adult females.
Technical Abstract: Our objective was to investigate the effects of variation in the leptin [LEP (19A>G)] and melanocortin-4 receptor [MC4R (V103I)] genes on obesity-related traits in 13 405 African-American (AA) and white participants from the Atherosclerosis Risk in Communities (ARIC) Study. We tested the association between the single-locus and multilocus genotypes and obesity-related measures [body mass index (BMI), body weight (BW), waist-hip ratio, waist circumference and leptin levels], adjusted for age, physical activity level, smoking status, diabetic status, prevalence of coronary heart disease, hypertension, stroke or transient ischaemic attack. AA and white female carriers of the MC4R I103 allele exhibited significantly lower BW than non-carriers of this allele (p < 0.05 and p < 0.01 respectively). AA female carriers of both the LEP A19 allele and the MC4R I103 allele were 63% [odds ratio (OR) = 0.37, 95% confidence interval (CI) (0.18-0.78)] less likely to be obese, and white female carriers of the same two alleles were 46% [OR = 0.54, 95% CI (0.32-0.91)] less likely to be obese, than non-carriers of the variant alleles. Female carriers of both the LEP A19 and MC4R I103 alleles had significantly lower BW (p < 0.05), BMI (p < 0.05), and plasma leptin (p < 0.01) than the non-carriers of both the alleles. Carriers of the two variant alleles had lower BMI over the 9-year course of the ARIC study and significantly lower weight gain from age 25 years. No significant joint effect of these two variants was observed in males. These results suggest that variation within the LEP and MC4R genes is associated with reduced risk for obesity in females.