Genetic variation and decreased risk for obesity in the Atherosclerosis Risk in Communities Study.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These results suggest that variation within the LEP and MC4R genes is associated with reduced risk for obesity in females.
Hart Sailors
M L
ML
Department of Pediatrics, Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA.
Folsom
A R
AR
Ballantyne
C M
CM
Hoelscher
D M
DM
Jackson
A S
AS
Linda Kao
W H
WH
Pankow
J S
JS
Bray
M S
MS
D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics*; D015992:Body Mass Index; D049628:Body Size; D053455:Caspase 10 / Q000235:genetics; D017931:DNA Primers; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups; D012307:Risk Factors; D012727:Sex Characteristics
D017931:DNA Primers; D020738:Leptin; D053455:Caspase 10