A Common Variant and the Transcript Levels of MC4R Gene Are Associated With Adiposity in Children: The IDEFICS Study

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Abstract

Context:

The melanocortin-4 receptor gene (MC4R) plays a pivotal role in the regulation of body fat and food and energy intake.

Objectives:

The objectives of the study were as follows: 1) to evaluate the association of variants rs17782313 and rs17700633 near the coding region of MC4R and 2) to evaluate the association of the transcript levels of MC4R with adiposity indices and percentage of energy from fat, carbohydrates, and protein in children.

Design:

The Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants (IDEFICS) cohort was used, with examinations at baseline (T0) and after 2 years (T1).

Setting and Participants:

A total of 16 228 schoolchildren (2–9 y) from eight European countries participated in the study. A random sample of 4381 children genotyped for MC4R variants and a subsample of 410 children with MC4R expression data in peripheral blood cells (PBCs) were included in the analyses.

Main Outcome Measures:

Anthropometric measures and energy intake (total and from fat, carbohydrates, and protein) served as outcomes for adiposity status and for dietary behavior, respectively.

Results:

At T0, the C allele of rs17782313 (minor frequency allele 23%) was significantly associated with higher values of adiposity indices (all P < .001). No association was found between rs17700633 (minor frequency allele 28%) and the variables under study. At T1, the C allele of rs17782313 was associated with a significantly higher increase in the adiposity indices over time (all P < .05). The MC4R expression levels in PBCs were inversely associated with body fat and energy intake from carbohydrates and directly with energy from fat (all P ≤ .05) but were not influenced by variants rs17782313 and rs17700633.

Conclusions:

The common variant rs17782313 near MC4R was cross-sectionally and longitudinally associated with body mass index and measures of body fatness in children aged 2–9 years. We showed, for the first time in humans, that MC4R expression levels in PBCs are related to body fat distribution and percentage of energy intake from carbohydrates and fat.

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