Lifestyle Intervention in Obese Children With Variations in the Melanocortin 4 Receptor Gene

Abstract

Because information on weight changes after lifestyle intervention in children with mutations in the melanocortin 4 receptor (MC4R) gene is scarce, we compared weight changes after lifestyle intervention between children with and without MC4R variations. A group of 514 overweight children (aged 5-16 years), who presented to participate in a 1-year lifestyle intervention based on exercise, behavior, and nutrition therapy were screened for MC4R mutations. For comparison, children with MC4R mutations leading to reduced receptor function (group A) were each of them randomly matched with five children of same age and gender without MC4R mutations (group B). Changes of weight status were analyzed as change of BMI standard deviation scores (BMI-SDSs). Furthermore, 16 children (3.1%) harbored MC4R mutations leading to reduced receptor function, and 17 (3.3%) children carried variations not leading to reduced receptor function. Children with and without MC4R mutations reduced their overweight at the end of intervention to a similar degree (P = 0.318 between groups based on an intention-to-treat analysis). The maintenance of weight loss after intervention among children with MC4R mutations leading to reduced receptor function failed in contrast to children without such mutations (P < 0.001 adjusted for BMI-SDS at baseline, age, and gender in an intention-to-treat analysis). In conclusion, children with MC4R mutations leading to reduced receptor function were able to lose weight in a lifestyle intervention but had much greater difficulties to maintain this weight loss supporting the impact of these mutations on weight status.