Polymorphisms in the leptin and leptin receptor genes in relation to resting metabolic rate and respiratory quotient in the Quebec Family Study

Background: Leptin (LEP) is an endocrine hormone that participates in many metabolic pathways, including those associated with the central regulation of energy homeostasis. Objective: We examined the associations between polymorphisms in the LEP and leptin receptor (LEPR) genes and resting metabolic rate (RMR) and respiratory quotient (RQ) in the Quebec Family Study. Methods and subjects: Three polymorphisms in LEPR (K109R, Q223R and K656N) and one in LEP (19A > G) were genotyped in 678 subjects. RMR, RQ at rest and RQ while sitting, standing and walking at 4.5 km/h (RQ45) were adjusted for age, sex, fat mass and fat-free mass. Results: RQ45 was associated with the LEPR-K109R ( P = 0.004) and Q223R ( P = 0.03) polymorphisms, and RMR showed association with the LEPR-K656N polymorphism ( P = 0.006). For the LEP-19A > G polymorphism, no significant associations were observed. However, LEP-A19A homozygotes who were carriers of the LEPR N656 allele had a significantly lower RQ45 compared to other genotype combinations (P for interaction = 0.003). Conclusion: These findings suggest that DNA sequence variation in the LEPR gene contributes to human variation in RMR and in the relative rates of substrate oxidation during low-intensity exercise in steady state but not in a resting state.