Rs12970134 near MC4R is associated with appetite and beverage intake in overweight and obese children: A family-based association study in Chinese population

Abstract

BackgroundRecent studies indicated that eating behaviors are under genetic influence, and the melanocortin 4 receptor (MC4R) gene polymorphisms can affect the total energy intake and the consumption of fat, protein and carbohydrates. Our study aims at investigating the association of the MC4R polymorphism with appetite and food intake among Chinese children.MethodsA family-based association study was conducted among 151 Chinese trios whose offsprings were overweight/obese children aged 9–15 years. The rs12970134 near MC4R was genotyped, and the Children Eating Behavior Questionnaire (CEBQ) and a self-designed questionnaire measuring food intake were performed. The FBAT and PBAT software packages were used.ResultsThe family-based association analysis showed that there was a significant association between rs12970134 and obesity (Z = 2.449, P = 0.014). After adjusting for age, gender and standardized BMI, rs12970134 was significantly associated with food responsiveness (FR) among children (β'b = 0.077, Pb = 0.028), and with satiety responsiveness (SR) in trios (P = -0.026). The polymorphism was associated with beverage intake (β'b = 0.331, Pb = 0.00016 in children; P = 0.043 in trios), but not significantly associated with vegetable, fruit or meat intake (P>0.050). We further found a significant mediation effect among the rs12970134, FR and beverage intake (b = 0.177, P = 0.047).ConclusionsOur study is the first to report that rs12970134 near MC4R was associated with appetite and beverage intake, and food responsiveness could mediate the effect of rs12970134 on beverage intake in overweight and obese Chinese children population. Further studies are needed to uncover the genetic basis for eating behaviors, which could lead to develop and implement effective interventional strategies early in life.

The MC4R genetic variants are associated with lower visceral fat accumulation and higher postprandial relative increase in carbohydrate utilization in humans

“…Only few studies have been attempted so far and results are conflicting. Some authors suggest that SNPs 12970134 influences energy and dietary fat intake [24,25], as well as eating behaviors [26], while other authors suggest that rs12970134 nor rs17782313 near the MC4R gene do not influence food intake, nor preferences for specific food items [21]. It is already known that interactions between MC4R gene with diet play a significant role in obesity and T2DM development [27], but the mechanisms by which different variants of SNPs near MC4R gene may influence the metabolic changes that lead to obesity, have not been known particularly yet.…”

Dietary Behaviours May Modulate the Association Between Common MC4R Genetic Variants and Obesity and Its Comorbidities: The 1000PLUS Cohort Study.

“…However, in carriers of the protective genotypes, dietary carbohydrate intake providing more than 48% of total energy may have even bene cial metabolic effects. Wang et al (33) found that in overweight and obese children, rs12970134 is associated with appetite and beverage intake, which could indicate that rs12970134 SNPs may possibly increase adiposity by affecting eating behaviours. Nevertheless, in our study we observed higher BMI and body fat content without noting any differences in daily energy and macronutrient intake between genotypes.…”

“…Activation of melanocortin system increases energy expenditure, insulin sensitivity and may in uence food intake regulation (11,32). Several studies have demonstrated that SNPs near the MC4R gene in uence appetite (33) as well as energy level and dietary fat intake (28,33); however, other studies have indicated that SNPs near the MC4R gene do not in uence food intake (34) and may not have any impact on body weight (35). These con icting results may be due to the fact that MC4R may be dependent on dietary intake: one study found that MC4R expression levels in peripheral blood cells (PBCs) in children were associated with the percentage of energy intake from carbohydrates and fat (36).…”

Genes and Eating Preferences, Their Roles in Personalized Nutrition

“…The MC4R gene encodes the protein, which is a membrane-bound receptor that plays an important role in energy homeostasis and eating preferences regulation. The protein, in association with melantropin, becomes responsible for the feeling of saturation [94]. In addition, the MC4R gene plays a key role in the regulation of glucose homeostasis [95].…”