title: The 3'-UTR of the adiponectin Q gene harbours susceptibility loci for atherosclerosis and its metabolic risk traits.
abstract: BACKGROUND
  Adiponectin Q is a hormone that modulates several metabolic processes and contributes to the suppression of biochemical pathways leading to metabolic syndrome. Hence, polymorphic changes in the adiponectin Q (ADIPOQ) gene are likely to contribute to metabolic disorders, and consequently lead to atherosclerosis. In the present study, we performed a population-based association study for 8 SNPs in 4646 Saudi individuals (2339 CAD cases versus angiographed 2307 controls) by real-time PCR.
  
  
  METHODS
  Linkage analysis was done by the Affymetrix Gene Chip array, sequencing by the MegaBACE DNA analysis system and genotyping accomplished by TaqMan chemistry with the Applied Biosystem real-time Prism 7900HT Sequence Detection System.
  
  
  RESULTS
  The rs2241766 (TG + GG) [Odds ratio(95% Confidence Interval = 1.35(1.01-1.72); p = 0.015] and rs9842733A > T [1.48(1.01-2.07); p = 0.042] were associated with hypertension [HTN; 3541 cases vs 1101 controls), following adjustment for the presence of other cardiovascular risk traits. The rs2241766 (TG + GG) was further implicated in harbouring of low high density lipoprotein levels (LHDL; 1353 versus 2156 controls) [1.35(1.10-1.67); p = 0.005], but lost its association with obesity after the adjustment for confounders. Besides, low high density lipoprotein was also linked with rs6444174 (TC + CC) [1.28(1.05-1.59)]. On the other hand, while initial univariate logistic regression analysis pointed to rs1063537 C > T (p = 0.010), rs2082940 C > T (p = 0.035) and rs1063539 G > C (p = 0.035) as being associated with myocardial infarction, significance levels of these relationships were diminished following adjustment for the influence of confounding covariates. Interestingly, haplotyping showed that an 8-mer haplotype GTGCCTCA and several of its derivatives constructed from the studied SNPs were commonly implicated in MI (χ² = 4.12; p = 0.042), HTN (χ² = 6.40; p = 0.011) and OBS (χ² = 5.18; p = 0.023).
  
  
  CONCLUSIONS
  These results demonstrate that the ADIPOQ 3'UTR harbours common susceptibility variants for metabolic risk traits and CAD, pointing to the importance of this region in atherosclerosis disease pathways.
authors: Nzioka
authors: N
authors: Muiya
authors: Mohammed
authors: M
authors: Al-Najai
authors: Asma I
authors: AI
authors: Tahir
authors: Samar
authors: S
authors: Elhawari
authors: Daisy
authors: D
authors: Gueco
authors: Editha
authors: E
authors: Andres
authors: Nejat
authors: N
authors: Mazhar
authors: Nada
authors: N
authors: Altassan
authors: Brian F
authors: BF
authors: Meyer
authors: Maie
authors: M
authors: Alshahid
authors: Genetics Department, King Faisal Specialist Hospital and Research Centre, P,O, Box 3354, Riyadh 11211, Saudi Arabia. dzimiri@kfshrc.edu.sa.
authors: Nduna
authors: N
authors: Dzimiri
mesh_terms: D020413:3' Untranslated Regions; D052242:Adiponectin / Q000235:genetics*; D018912:Arabs / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D008875:Middle Aged; D012529:Saudi Arabia
chemical_list: D020413:3' Untranslated Regions; C499918:ADIPOQ protein, human; D052242:Adiponectin; D008075:Lipoproteins, HDL