CHILDHOOD OBESITY: REGULATION OF ENERGY BALANCE AND BODY COMPOSITION
Location: Children Nutrition Research Center (Houston, Tx)
Title: Association of MC4R variants with obesity-related traits in Hispanic children
| Voruganti, V - |
| Cai, Guowen - |
| Haack, Karin - |
| Cole, Shelley - |
| Butte, Nancy - |
| Comuzzie, Anthony - |
Submitted to: Obesity
Publication Type: Abstract Only
Publication Acceptance Date: September 1, 2008
Publication Date: October 1, 2008
Citation: Voruganti, V.S., Cai, G., Haack, K., Cole, S.A., Butte, N., Comuzzie, A. 2008. Association of MC4R variants with obesity-related traits in Hispanic children [abstract]. Obesity. 16:956-P(Suppl. 1).
Melanocortin 4 receptor (MC4R) has been implicated in the regulation of appetite and energy expenditure. In children, MC4R mutations have been associated with severe obesity. The main objective of this study was to investigate the potential functional effects of variants in MC4R gene on the variation in obesity-related traits in Hispanic children from the Viva La Familia study. The MC4R gene and its flanking regions were resequenced in 1030 children. The association between genotypes and traits related to obesity (BMI, waist circumference, fat mass, fat percent, and circulating levels of ghrelin, glucose, and insulin) were tested using measured genotype analysis. Bayesian quantitative trait nucleotide (BQTN) analysis was used to test for functional variants. All analyses were conducted adjusting for age, sex, age*sex in the software program SOLAR. Twenty-five single nucleotide polymorphisms (SNPs) were identified, six in the exon, ten downstream, and nine upstream of the exon. In the exon, G55V mutation was associated with higher BMI (31 vs. 25 kg/m2, p < 0.05), and L mutation was associated with significantly higher glucose levels (105 vs. 92 mg/dl, p < 0.01). Downstream of the exon, the T/C allele of a flanking SNP was associated with higher glucose levels than the T/T allele (126 vs. 91 mg/dl, p < 0.001). Upstream of the exon, the A/G allele of a SNP was associated with lower BMI z score, fat mass, and waist circumference than the G/G allele (p < 0.05). The A/C allele of rs34114122, upstream of the exon, was associated with higher BMI z score and percent fat and lower serum ghrelin levels (p < 0.05) than the A/A allele. Adjusting for multiple testing, the association of rs34114122 with serum ghrelin remained significant (p = 0.002). The BQTN analysis showed a strong functional effect for rs34114122 in the regulation of variation in serum ghrelin levels (posterior probability of a functional effect = 0.81). In summary, novel SNPs in the MC4R gene were associated with obesity-related traits in Hispanic children.