Polymorphisms in the leptin and leptin receptor genes in relation to resting metabolic rate and respiratory quotient in the Québec 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
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).


CONCLUSIONS
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.
Loos
R J F
RJ
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Rankinen
T
T
Chagnon
Y
Y
Tremblay
A
A
Pérusse
L
L
Bouchard
C
C
D000328:Adult; D000886:Anthropometry; D001481:Basal Metabolism / Q000235:genetics*; D015444:Exercise / Q000502:physiology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000502:physiology; D010641:Phenotype; D011110:Polymorphism, Genetic; D011659:Pulmonary Gas Exchange / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin
C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin