title: Association of the angiotensinogen gene polymorphism with atherosclerosis and its risk traits in the Saudi population.
abstract: BACKGROUND
  Angiotensinogen (AGT) constitutes a central component of the renin-angiotensin system that controls the systemic blood pressure and several other cardiovascular functions and may play an important role in atherosclerosis pathways. In this study, we employed TaqMan genotyping assays to evaluate the role of 8 AGT variants in primary hypertension (HTN), type 2 diabetes mellitus (T2DM), and obesity as a possible trigger of coronary artery disease (CAD) in a population of 4615 angiographed native Saudi individuals.
  
  
  METHODS
  Linkage analysis was done by using the Affymetrix Gene Chip array, sequencing by using the MegaBACE DNA analysis system and genotyping accomplished by TaqMan chemistry using the Applied Biosystem real-time Prism 7900HT Sequence Detection System.
  
  
  RESULTS
  Six variants, rs2067853 GG [Odds ratio(95% Confidence Interval) = 1.44(1.17-1.78); p = 0.001], rs7079 [1.49(1.20-1.85); p < 0.0001], rs699 G [1.19(1.08-1.13); p < 0.0001], rs3789679 A [1.51(1.14-1.99); p = 0.004], rs2148582 GG [1.31(1.11-1.55); p = 0.002] and rs5051 TC + CC [1.32(1.13-1.60); p = 0.001] conferred risk for HTN (3521 cases versus 1094 controls). The rs2067853 (p = 0.042), rs699G (p = 0.007) and rs5051 (p = 0.051) also conferred risk for myocardial infarction (MI; 2982 vs 1633), while rs3789679 A (p < 0.0001) and GA + AA (p < 0.0001) as well as rs4762G (p = 0.019) were associated with obesity (1576 vs 2458). However, while these variants appeared to be also associated with CAD (2323 vs 2292), only the rs7079G (p = 0.035) retained its significant relationship. Interestingly, among the haplotypes constructed from these SNPs, the baseline 8-mer haplotype, GGTGGGGT (χ² = 7.02; p = 0.0081) and another GGCGGAGT (χ² = 5.10; p = 0.024), together with several of their derivatives were associated with HTN. T2DM was associated with two 8-mer haplotypes, GGTAGGAC (χ2 = 5.66; p = 0.017) and ATTGAGAC (χ² = 5.93; p = 0.015), obesity with GGCGGAGT (χ² = 9.49; p = 0.0021) and MI was linked to ATTGGGAC (χ² = 6.68; p = 0.010) and GGTGGGAT (χ² = 4.25; p = 0.039). Furthermore, several causative haplotypes were also shared among the risk traits as well as with CAD.
  
  
  CONCLUSIONS
  These results point to AGT as independently conferring risk for various cardiovascular traits, and possibly interacting with these traits in events leading to atherosclerosis.
authors.affiliation: Genetics Department, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Najai
authors.forename: Paul
authors.initials: P
authors.lastname: Muiya
authors.forename: Asma I
authors.initials: AI
authors.lastname: Tahir
authors.forename: Samar
authors.initials: S
authors.lastname: Elhawari
authors.forename: Daisy
authors.initials: D
authors.lastname: Gueco
authors.forename: Editha
authors.initials: E
authors.lastname: Andres
authors.forename: Nejat
authors.initials: N
authors.lastname: Mazhar
authors.forename: Nada
authors.initials: N
authors.lastname: Altassan
authors.forename: Maie
authors.initials: M
authors.lastname: Alshahid
authors.forename: Nduna
authors.initials: N
authors.lastname: Dzimiri
mesh_terms: D000808:Angiotensinogen / Q000235:genetics*; D018912:Arabs / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D012529:Saudi Arabia / Q000453:epidemiology
chemical_list: D000808:Angiotensinogen