POLYMORPHISMS IN THE MELANOCORTIN-4 RECEPTOR IN RELATION TO PHYSICAL INACTIVITY IN THE QUEBEC FAMILY STUDY

Physical inactivity is an important risk factor for a range of chronic diseases. Despite efforts to promote physical activity in the population, most people are sedentary. Low compliance to interventions suggests that biological systems, such as the arcuate nucleus in the hypothalamus, which controls energy homeostasis and behavior, may be involved in exercise adherence. PURPOSE To examine the association between sequence variations in the melanocortin-4 receptor (MC4R) gene and physical inactivity in the Quebec Family Study. METHODS We genotyped two polymorphisms of the MC4R gene in 642 subjects (from 190 families, age (X±SD): parents: 53±7.3 yrs, offspring: 28±8.5 yrs) by using polymerase chain reaction amplification followed by digestion with the restriction enzymes NcoI and HincII. The level of physical inactivity was estimated by a three-day diary and the physical inactivity score was adjusted for gender, age and BMI. Associations between the physical inactivity score and the MC4R polymorphisms were analyzed using the MIXED procedure of the SAS software package. RESULTS The NcoI polymorphism showed significant (p = 0.01) association with physical inactivity, with the highest inactivity score for the 5.6 kb/5.6 kb genotype (table). When obese subjects were excluded, the association was even more pronounced (p = 0.007). For the HincII polymorphism, no significant association was observed.Table: No Caption AvailableCONCLUSION These findings suggest that DNA sequence variation in the MC4R gene locus could contribute to the propensity to be sedentary, particularly among the non-obese subjects.