title: Causal relationship between adiponectin and metabolic traits: a Mendelian randomization study in a multiethnic population.
abstract: BACKGROUND
  Adiponectin, a secretagogue exclusively produced by adipocytes, has been associated with metabolic features, but its role in the development of the metabolic syndrome remains unclear.
  
  
  OBJECTIVE
  We investigated the association between serum adiponectin level and metabolic traits, using both observational and genetic epidemiologic approaches in a multiethnic population assembled in Canada.
  
  
  METHODS
  Clinical data and serum adiponectin level were collected in 1,157 participants of the SHARE/SHARE-AP studies. Participants were genotyped for the functional rs266729 and rs1260326 SNPs in ADIPOQ and GCKR genes.
  
  
  RESULTS
  Adiponectin level was positively associated with HDL cholesterol and negatively associated with body mass index, waist-to-hip ratio, triglycerides, fasting glucose, fasting insulin, systolic and diastolic pressure (all P<0.002). The rs266729 minor G allele was associated with lower adiponectin and higher HOMA-IR (P = 0.004 and 0.003, respectively). The association between rs266729 SNP and HOMA-IR was no longer significant after adjustment for adiponectin concentration (P = 0.10). The rs266729 SNP was associated with HOMA-IR to an extent that exceeded its effect on adiponectin level (0.15 SD 95% C.I. [0.06, 0.24], P<0.001). There was no significant interaction between rs266729 SNP and ethnicity on adiponectin or HOMA-IR. In contrast, the SNP rs1260326 in GCKR was associated with HOMA-IR (P<0.001), but not with adiponectin level (P = 0.67).
  
  
  CONCLUSIONS
  The association of the functional promoter polymorphism rs266729 with lower serum adiponectin and increased insulin resistance in diverse ethnic groups may suggest a causal relationship between adiponectin level and insulin resistance.
authors.affiliation: Population Health Research Institute, Hamilton, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mente
authors.forename: David
authors.initials: D
authors.lastname: Meyre
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Lanktree
authors.forename: Mahyar
authors.initials: M
authors.lastname: Heydarpour
authors.forename: A Darlene
authors.initials: AD
authors.lastname: Davis
authors.forename: Ruby
authors.initials: R
authors.lastname: Miller
authors.forename: Hertzel
authors.initials: H
authors.lastname: Gerstein
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics*; D000328:Adult; D000368:Aged; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D057182:Mendelian Randomization Analysis; D008660:Metabolism / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019655:Quantitative Trait, Heritable; D012044:Regression Analysis
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin