Common genetic variation near MC4R is associated with eating behaviour patterns in European populations

Abstract

Both rs17782313 (near MC4R) and rs1421085 (FTO) polymorphisms have been consistently associated with increased risk of obesity and with body mass index (BMI) variation. An effect of both polymorphisms on satiety has recently been suggested. We genotyped rs17782313 and rs1421085 in 5764 relatives from 1109 French pedigrees with familial obesity, 1274 Swiss class III obese adults as well as in 4877 French adults and 5612 Finnish teenagers from two randomly selected population cohorts. In all subjects, eating behaviour traits were documented through questionnaires. We first assessed the association of both single nucleotide polymorphisms with BMI and then studied eating behaviour. Under an additive model, the rs17782313-C MC4R allele showed a trend towards higher percentages of snacking in both French obese children (P ¼ 0.01) and Swiss obese adults (P ¼ 0.04) as well as in adolescents from the Finnish general population (P ¼ 0.04). In French adults with familial obesity, this allele tended to be also associated with a higher Stunkard hunger score (P ¼ 0.02) and in obese children with a higher prevalence of eating large amounts of food (P ¼ 0.04). However, no consistent association of the FTO rs1421085-C allele and available eating behaviour trait was found in our studied populations. The rs17782313-C allele nearby MC4R may modulate eating behaviour-related phenotypes in European obese and randomly selected populations, in both children and adults, supporting a regulatory role of this genetic variant on eating behaviour, as previously shown for MC4R non-synonymous loss-offunction mutations. The potential effect of the obesity-associated FTO gene on eating behaviour deserves additional investigation.

Association of melanocortin 4 receptor gene variation with satiation and gastric emptying in overweight and obese adults

“…Thus, it is conceivable that individuals with rs17782313(C) polymorphism may ingest more frequent meals, resulting in a higher daily caloric intake. Therefore, our findings extend the observations of prior population studies (Beckers et al 2011;Qi et al 2008;Stutzmann et al 2009;Valladares et al 2010;Vogel et al 2011;Xi et al 2012) and suggest that rs17782313(C) polymorphism may be associated with higher BMI due to decreased postprandial satiation symptoms. Additionally, we report that the individuals with rs17782313(C) polymorphism had a 6.7 and 3.2 % slower GE of solids at 2 and 4 h, respectively, when compared with individual with the TT genotype.…”

“…In population studies, the gene variation rs17782313 (nearest gene, MC4R) has been associated with higher BMI and food intake (Beckers et al 2011;Qi et al 2008;Stutzmann et al 2009;Valladares et al 2010;Vogel et al 2011;Xi et al 2012). In this study in humans, we explored the associations of this gene variation with gastric motor function, satiation, and satiety.…”

“…The average increase in BMI was 0.22 kg/m 2 . The polymorphism rs17782313 is associated with satiety in American, European, and Chilean children (Beckers et al 2011;Czerwensky et al 2013;Qi et al 2008;Stutzmann et al 2009;Valladares et al 2010;Xi et al 2012) as well as with higher intake of total calories, fat, and protein (Beckers et al 2011;Loos 2011;Qi et al 2008;Scherag et al 2010;Valette et al 2013). In a systematic review of 61 studies (involving 80,957 obese and 220,223 controls), rs17782313 polymorphism was significantly associated with obesity risk (OR 1.18, 95 % CI 1.15-1.21, p = 0.001) (Xi et al 2012).…”

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

“…Consistent with this observation is evidence from the ALSPAC study using 3 day dietary records, where children (10-11years) carrying the risk allele for FTO ingested more energy and specifi cally more dietary fat than those not carrying the risk allele (Timpson et al, 2008). These fi ndings contrast with at least three studies which report no associations with energy intake in children (Hakanen et al, 2009;Okuda et al, 2011;Stutzmann et al, 2009) and to the observation in mice that FTO may modulate energy homeostasis through energy expenditure (Fischer et al, 2009;Speakman, 2010). However, several studies, including a large meta-analysis have recently shown that energy expenditure through activity appears to attenuate the genetic susceptibility to overweight and obesity from FTO in children Scott et al, 2010) and adults (Andreasen et al, 2008;Kilpelainen et al, 2011).…”

Fat brains, greedy genes, and parent power: A biobehavioural risk model of child and adult obesity

“…Wardle et al (2009) found that 4 -5 year olds homozygous for the low-risk T allele ate signifi cantly less than children heterozygous or homozygous for the high-risk A allele and demonstrated that the high-risk allele was associated with lower levels of parent-reported satiety sensitivity , while Tanofsky-Kraff et al (2009) reported that children with 1 or 2 (versus 0) high-risk alleles were more likely to experience loss of control and have greater intake of fat during an eating episode. Variants near MC4R (Stutzmann et al, 2009) as well as other common variants ( SH2B1, KCTD15, MTCH2, NEGR1, BDNF ) (Bauer et al, 2009), may also be associated with increased intake of highenergy foods.…”