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

Abstract

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.

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Acknowledgements

The Québec Family Study was supported by multiple grants from the Medical Research Council of Canada and the Canadian Institutes for Health Research (PG-11811, MT-13960 and GR-15187). R Loos is supported by a postdoctoral fellowship from the American Heart Association; Southeast affiliate (no. 0325355B). C Bouchard is partially supported by the George A Bray Chair in Nutrition.

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Loos, R., Rankinen, T., Chagnon, Y. et al. Polymorphisms in the leptin and leptin receptor genes in relation to resting metabolic rate and respiratory quotient in the Québec Family Study. Int J Obes 30, 183–190 (2006). https://doi.org/10.1038/sj.ijo.0803127

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