title: Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program.
abstract: OBJECTIVE
  Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population.
  
  
  METHODS
  Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling.
  
  
  RESULTS
  Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions of rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with ∼18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations.
  
  
  CONCLUSIONS
  ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations.
authors.affiliation: Division of Endocrinology and Metabolism, Indiana University, Indianapolis, IN, USA. dppmail@biostat.bsc.gwu.edu
authors.forename: K J
authors.initials: KJ
authors.lastname: Mather
authors.forename: C A
authors.initials: CA
authors.lastname: Christophi
authors.forename: K A
authors.initials: KA
authors.lastname: Jablonski
authors.forename: W C
authors.initials: WC
authors.lastname: Knowler
authors.forename: R B
authors.initials: RB
authors.lastname: Goldberg
authors.forename: S E
authors.initials: SE
authors.lastname: Kahn
authors.forename: T
authors.initials: T
authors.lastname: Spector
authors.forename: Z
authors.initials: Z
authors.lastname: Dastani
authors.forename: D
authors.initials: D
authors.lastname: Waterworth
authors.forename: J B
authors.initials: JB
authors.lastname: Richards
authors.forename: T
authors.initials: T
authors.lastname: Funahashi
authors.forename: F X
authors.initials: FX
authors.lastname: Pi-Sunyer
authors.forename: T I
authors.initials: TI
authors.lastname: Pollin
authors.forename: J C
authors.initials: JC
authors.lastname: Florez
authors.forename: P W
authors.initials: PW
authors.lastname: Franks
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016016:Proportional Hazards Models; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D054419:Receptors, Adiponectin