title: Variants in adiponectin signaling pathway genes show little association with subclinical CVD in the diabetes heart study.
abstract: OBJECTIVE
  Understanding the interplay between adiposity, inflammation, and cardiovascular complications in type 2 diabetes mellitus (T2DM) remains a challenge. Signaling from adipocytes is considered important in this context. Adiponectin is the most abundant adipocytokine and has been associated with various measures of cardiovascular disease (CVD). This study examines the relationships between genetic variants in the adiponectin (ADIPOQ) and adiponectin-related signaling pathway genes and measures of subclinical CVD (vascular calcified plaque and carotid intima-media thickness), plasma lipids, and inflammation in T2DM.
  
  
  METHODS
  Single-nucleotide polymorphisms (SNPs) in ADIPOQ (n = 45), SNPs tagging ADIPOR1 (n = 6), APIPOR2 (n = 8), APPL1 (n = 6) and known rare coding variants in KNG1 (n = 3) and LYZL1 (n = 3) were genotyped in 1220 European Americans from the family-based Diabetes Heart Study. Associations between SNPs and phenotypes of interest were assessed using a variance components analysis with adjustment for age, sex, T2DM-affected status, and body mass index.
  
  
  RESULTS
  There was minimal evidence of association between SNPs in the adiponectin signaling pathway genes and measures of calcified plaque; eight of the 71 SNPs showed evidence of association with subclinical CVD (P = 0.007-0.046) but not with other phenotypes examined. Nine additional SNPs were associated with at least one of the plasma lipid measures (P = 0.008-0.05).
  
  
  CONCLUSIONS
  Findings from this study do not support a significant role for variants in the adiponectin signaling pathway genes in contributing to risk for vascular calcification in T2DM. However, further understanding the interplay between adiposity, plasma lipids, and inflammation may prove important in the prediction and management of cardiovascular complications in T2DM.
authors.affiliation: Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cox
authors.forename: John E
authors.initials: JE
authors.lastname: Lambird
authors.forename: S Sandy
authors.initials: SS
authors.lastname: An
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D052242:Adiponectin / Q000235:genetics*; D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D048909:Diabetes Complications / Q000235:genetics / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008055:Lipids / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000235:genetics; D009765:Obesity / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D061205:Vascular Calcification / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; C464801:APPL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin; D008055:Lipids; D054419:Receptors, Adiponectin; D009113:Muramidase