title: Adiponectin and adiponectin receptor gene variants in relation to resting metabolic rate, respiratory quotient, and adiposity-related phenotypes in the Quebec Family Study.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ruchat
authors.forename: Tuomo
authors.initials: T
authors.lastname: Rankinen
authors.forename: Angelo
authors.initials: A
authors.lastname: Tremblay
authors.forename: Louis
authors.initials: L
authors.lastname: Pérusse
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001481:Basal Metabolism / Q000235:genetics* / Q000502:physiology; D001823:Body Composition / Q000235:genetics*; D050218:Body Fat Distribution; D015992:Body Mass Index; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011792:Quebec; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface