Adiponectin and adiponectin receptor gene variants in relation to resting metabolic rate, respiratory quotient, and adiposity-related phenotypes in the Québec Family Study

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, −3882T→C) and ADIPOR2 (ie, IVS1 −1352G→A) 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 (−3971A→G) and ADIPOR1 (−3882T→C). 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 45T→G variant contributes to overall fatness and abdominal obesity are confirmed. Moreover, variants in the promoter region of both ADIPOR genes contribute to substrate oxidation.