PurposeA common variant of the melatonin receptor 1B (MTNR1B) gene has been related to increased signaling of melatonin, a hormone previously associated with body fatness mainly through effects on energy metabolism. We examined whether the MTNR1B variant affects changes of body fatness and composition in response to a dietary weight loss intervention.MethodsThe MTNR1B rs10830963 variant was genotyped for 722 overweight and obese individuals, who were randomly assigned to one of four diets varying in macronutrient composition. Anthropometric and body composition measurements (DXA scan) were collected at baseline and at 6 and 24 months of follow-up.ResultsStatistically significant interactions were observed between the MTNR1B genotype and low-/high-fat diet on changes in weight, body mass index (BMI), waist circumference (WC) and total body fat (p interaction=0.01, 0.02, 0.002 and 0.04, respectively), at 6months of dietary intervention. In the low-fat diet group, increasing number of the sleep disruption-related G allele was significantly associated with a decrease in weight (p=0.004), BMI (p=0.005) and WC (p=0.001). In the high-fat diet group, carrying the G allele was positively associated with changes in body fat (p=0.03). At 2years, the associations remained statistically significant for changes in body weight (p=0.02), BMI (p=0.02) and WC (p=0.048) in the low-fat diet group, although the gene-diet interaction became less significant.ConclusionsThe results suggest that carriers of the G allele of the MTNR1B rs10830963 may have a greater improvement in body adiposity and fat distribution when eating a low-fat diet.