title: Common haplotypes at the adiponectin receptor 1 (ADIPOR1) locus are associated with increased risk of coronary artery disease in type 2 diabetes.
abstract: Adiponectin, an adipokine facilitating insulin action, has antiatherogenic effects. This study investigated whether common polymorphisms in the adiponectin receptor 1 (ADIPOR1) gene mediating these effects influence the risk of coronary artery disease (CAD) in type 2 diabetes. Linkage disequilibrium analysis of 28 single nucleotide polymorphisms (SNPs) spanning the entire ADIPOR1 locus revealed two haplotype blocks that could be tagged by six SNPs. These six markers were typed in two populations of CAD-positive and -negative subjects with type 2 diabetes, one from Boston (n = 411) and the other from Italy (n = 533). In the Boston population, the three tags of the more 3' block were all significantly associated with CAD (P = 0.001-0.01). A similar trend, although not significant, was found in Italian subjects. Haplotype analysis of the combined populations revealed different haplotype distributions in case and control subjects (P = 0.0002), with one common haplotype being associated in homozygotes with a greater than threefold increase in cardiovascular risk (odds ratio 3.6 [95% CI 1.8-7.2]). Some of the genotypes associated with increased cardiovascular risk were associated with 30-40% lower ADIPOR1 mRNA levels in blood mononuclear cells (n = 60) and adipose tissue biopsies (n = 28) (P = 0.001-0.014). Our findings point to genetic variability at the ADIPOR1 locus as a strong determinant of CAD susceptibility in type 2 diabetes.
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Soccio
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bacci
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mlynarski
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Placha
authors.forename: Greer
authors.initials: G
authors.lastname: Raggio
authors.forename: Rosa
authors.initials: R
authors.lastname: Di Paola
authors.forename: Antonella
authors.initials: A
authors.lastname: Marucci
authors.forename: Michael T
authors.initials: MT
authors.lastname: Johnstone
authors.forename: Ernest V
authors.initials: EV
authors.lastname: Gervino
authors.forename: Nada A
authors.initials: NA
authors.lastname: Abumrad
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Doria
mesh_terms: D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics*; D012306:Risk
chemical_list: C475418:ADIPOR1 protein, human; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface