FTO and MC4R gene variants determine BMI changes in children after intensive lifestyle intervention

ObjectivesThis study aimed to determine whether there is a relationship between common FTO (rs17817449) and MC4R (rs17782313) gene variants and body mass reduction or weight loss after a one-month lifestyle intervention in overweight/obese children.Design and methodsWe genotyped 357 unrelated non-diabetic Czech children (age 13.7 ± 4.9 years, average BMI at baseline 30.8 ± 4.6 kg/m2). Biochemical and anthropometrical measurements were performed before and after 4 weeks of lifestyle interventions (comprising a reduction in energy intake to the age-matched optimum and a supervised exercise program consisting of 5 exercise units per day, 50 min each).ResultsThe mean weight loss achieved was 6.2 ± 2.1 kg (P < 0.001). Significant associations were found between a BMI decrease and the FTO and MC4R variants. Carriers of the FTO GG genotype and/or MC4R CC genotype lost significantly more body weight compared to noncarriers (P < 0.0009 for BMI and P < 0.002 for body weight). These differences remained significant following adjustment for sex, age and baseline values (P = 0.004 for BMI and P = 0.01 for body weight).ConclusionsFTO and MC4R gene variants modify the impact of an intensive lifestyle intervention on BMI decrease in overweight/obese children. Carriers of the FTO GG genotype and MC4R CC genotype benefit significantly more from the lifestyle intervention.

► Polymorphisms of FTO and MC4R genes are important determinants of body weight.
► Rare FTO and MC4R alleles carriers respond better to lifestyle intervention.
► Negative genetic predisposition can be overrun by lifestyle measures.
► FTO and MC4R genotyping can help individualize lifestyle recommendations.