title: Adiponectin level as a consequence of genetic variation, but not leptin level or leptin: adiponectin ratio, is a risk factor for carotid intima-media thickness.
abstract: OBJECTIVE
  The adipocytokines adiponectin and leptin have been suggested as risk factors for cardiovascular disease, including stroke, acting through atherosclerosis. However, studies have provided conflicting results in underpowered cohorts with some suggesting that the leptin:adiponectin ratio is a better predictor of risk. We examined these associations with carotid intima-media thickness (IMT), a marker of early atherosclerosis and arterial remodeling and an independent predictor of stroke. We also examined association between genetic variants in the leptin and adiponectin genes and IMT.
  
  
  METHODS
  Adiponectin and leptin levels were determined in 990 individuals from the community Carotid Atherosclerosis Progression Study. Five variants in the gene encoding adiponectin and 7 in the gene encoding leptin were genotyped and their effects on circulating levels assessed. Both were then correlated with IMT.
  
  
  RESULTS
  Adiponectin levels negatively correlated with IMT (-0.079, P=0.013). There was no correlation between leptin levels or leptin:adiponectin ratio and IMT. Two variants in the ADIPOQ gene encoding adiponectin were associated with altered adiponectin levels, 1 of which (rs266729) was associated with IMT. There was also an interaction with body mass index (P=0.019) with the association being present in obese subjects (P=0.02).
  
  
  CONCLUSIONS
  Our results support a causal role for adiponectin in early carotid IMT and suggest it may act through interaction with obesity. In contrast, we found no evidence of a role for leptin and no evidence that leptin:adiponectin ratio is a better predictor of risk that adiponectin levels alone.
authors.affiliation: Stroke and Dementia Research Centre, Clinical Sciences, St George's University of London, Cranmer Terrace, Tooting, London SW17 0RE, UK. sbevan@sgul.ac.uk
authors.forename: Steve
authors.initials: S
authors.lastname: Bevan
authors.forename: Karina
authors.initials: K
authors.lastname: Meidtner
authors.forename: Matthias
authors.initials: M
authors.lastname: Lorenz
authors.forename: Matthias
authors.initials: M
authors.lastname: Sitzer
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Grant
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
mesh_terms: D052242:Adiponectin / Q000097:blood* / Q000235:genetics*; D000328:Adult; D000368:Aged; D015415:Biomarkers; D015992:Body Mass Index; D002340:Carotid Artery Diseases / Q000097:blood / Q000473:pathology; D014644:Genetic Variation; D006801:Humans; D020738:Leptin / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017539:Tunica Intima / Q000473:pathology*; D017540:Tunica Media / Q000473:pathology*
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D020738:Leptin