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Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children.

ABSTRACT: Melanocortin-4-receptor (MC4R) haploinsufficiency is the most common form of monogenic obesity; however, the frequency of MC4R variants and their functional effects in general populations remain uncertain.The aim was to identify and characterize the effects of MC4R variants in Hispanic children.MC4R was resequenced in 376 parents, and the identified single nucleotide polymorphisms (SNPs) were genotyped in 613 parents and 1016 children from the Viva la Familia cohort. Measured genotype analysis (MGA) tested associations between SNPs and phenotypes. Bayesian quantitative trait nucleotide (BQTN) analysis was used to infer the most likely functional polymorphisms influencing obesity-related traits.Seven rare SNPs in coding and 18 SNPs in flanking regions of MC4R were identified. MGA showed suggestive associations between MC4R variants and body size, adiposity, glucose, insulin, leptin, ghrelin, energy expenditure, physical activity, and food intake. BQTN analysis identified SNP 1704 in a predicted micro-RNA target sequence in the downstream flanking region of MC4R as a strong, probable functional variant influencing total, sedentary, and moderate activities with posterior probabilities of 1.0. SNP 2132 was identified as a variant with a high probability (1.0) of exerting a functional effect on total energy expenditure and sleeping metabolic rate. SNP rs34114122 was selected as having likely functional effects on the appetite hormone ghrelin, with a posterior probability of 0.81.This comprehensive investigation provides strong evidence that MC4R genetic variants are likely to play a functional role in the regulation of weight, not only through energy intake but through energy expenditure.

SUBMITTER: Cole SA

PROVIDER: S-EPMC2793108 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children.

Cole Shelley A SA Butte Nancy F NF Voruganti V Saroja VS Cai Guowen G Haack Karin K Kent Jack W JW Blangero John J Comuzzie Anthony G AG McPherson John D JD Gibbs Richard A RA

The American journal of clinical nutrition 20091104 1

<h4>Background</h4>Melanocortin-4-receptor (MC4R) haploinsufficiency is the most common form of monogenic obesity; however, the frequency of MC4R variants and their functional effects in general populations remain uncertain.<h4>Objective</h4>The aim was to identify and characterize the effects of MC4R variants in Hispanic children.<h4>Design</h4>MC4R was resequenced in 376 parents, and the identified single nucleotide polymorphisms (SNPs) were genotyped in 613 parents and 1016 children from the ...[more]

PMID: 19889825

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Project description:BackgroundDespite growing scientific interest in the benefits of breaking up sedentary time with intermittent standing or walking, few studies have investigated the energy cost of posture transitions. This study aimed to determine whether posture transitions are associated with increased energy expenditure in preschool children.MethodsForty children (mean age 5.3 ± 1.0y) completed a ~150-min room calorimeter protocol involving sedentary, light, and moderate- to vigorous-intensity activities. This study utilised data from ~65-min of the protocol, during which children were undertaking sedentary behaviours (TV viewing, drawing/colouring in, and playing with toys on the floor). Posture was coded as sit/lie, stand, walk, or other using direct observation; posture transitions were classified as sit/lie to stand/walk, sit/lie to other, stand/walk to other, or vice versa. Energy expenditure was calculated using the Weir equation and used to calculate individualised MET and activity energy expenditure (AEE) values. Spearman's rank correlations were used to compare the number of posture transitions, in the individual activities separately and combined, with corresponding MET and AEE values. Participants were divided into tertiles based on the number of posture transitions; MET and AEE values of children in the lowest and highest tertiles of posture transitions were compared using unpaired t-tests. Effect sizes (Cohen's d) were calculated.ResultsThere was a positive correlation between the total number of posture transitions and average METs (rs = 0.42, p = 0.02) and AEE (rs = 0.43, p = 0.02). MET differences between the lowest and highest tertiles of posture transitions resulted in a small effect size for playing with toys (d = 0.27), and moderate effect sizes for TV viewing, drawing and all three activities combined (d = 0.61, 0.50 and 0.64 respectively). Similar results were found for AEE.ConclusionsResults from this study showed that variation in posture transitions may be associated with variation in energy expenditure in preschool children. The findings suggest that the concept that variation in posture transitions may have meaningful biological or health effects in early childhood is worth investigating further.

Dataset Information

Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children.

Publications

Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children.

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