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ORIGINAL RESEARCH COMMUNICATION |
1 From the Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA (RJFL, TR, and CB), and the Department of Social and Preventive Medicine, Division of Kinesiology, Laval University, Ste-Foy, Canada (SR, AT, and LP)
Background: Despite adiponectin's presumed role in fatty acid oxidation and energy homeostasis, little is known about the effect of gene variants on substrate oxidation, energy expenditure, and adiposity-related phenotypes.
Objective: We examined the effects of genetic variation in adiponectin (ADIPOQ) and adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) on resting metabolic rate, respiratory quotient (RQ), and adiposity-related phenotypes.
Design: We studied the associations of ADIPOQ, ADIPOR1, and ADIPOR2 polymorphisms with resting metabolic rate, RQ, and body mass index, percentage body fat, sum of 6 skinfold thicknesses, waist circumference, and total, subcutaneous, and visceral fat in 759 participants in the Québec Family Study.
Results: The ADIPOQ 45T
G single-nucleotide polymorphism (SNP) was significantly (P = 0.0002 to 0.04) associated with overall adiposity and abdominal adiposity; the rare homozygotes (G/G) had a leaner phenotype than did the carriers of the common allele. One SNP each in the putative promoter of ADIPOR1 (ie, –3882TC) and ADIPOR2 (ie, IVS1 –1352GA) was associated with RQ (P = 0.03 and 0.04, respectively), and the association was even stronger in nonobese persons (P = 0.02 and 0.003). Carriers of the common alleles (ADIPOR1 T and ADIPOR2 G alleles) had a lower RQ than did the rare homozygotes. A significant genotype-by-genotype interaction (P = 0.0002 to 0.02) was found between SNPs in the promoters of ADIPOQ (–3971AG) and ADIPOR1 (–3882TC). Subjects carrying the minor ADIPOQ allele (G allele) who were rare homozygotes (C/C) for the ADIPOR1 SNP had a higher RQ (P = 0.003) and greater overall (P < 0.03) and abdominal (P < 0.05) adiposity than did persons with other genotype combinations.
Conclusions: Previous findings that the ADIPOQ 45TG variant contributes to overall fatness and abdominal obesity are confirmed. Moreover, variants in the promoter region of both ADIPOR genes contribute to substrate oxidation.
Key Words: Adiponectin • adiponectin receptor • resting metabolic rate • respiratory quotient • obesity • abdominal obesity • adiposity
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