title: Multifactor dimensionality reduction analysis of MTHFR, PAI-1, ACE, PON1, and eNOS gene polymorphisms in patients with early onset coronary artery disease.
abstract: BACKGROUND
  Association studies in the Turkish population have investigated the single locus effects of different gene polymorphisms on coronary artery disease (CAD). CAD is a complex polygenic disease that involves complex interactions among multiple genetic and environmental conditions.
  
  
  METHODS
  We evaluated associations of five candidate genetic polymorphisms (methylene tetrahydrofolate reductase C677T, plasminogen activator inhibitor 4G/5G, endothelial nitric oxide synthase (eNOS) 3-27 base pair repeat, insertion, or deletion of a 287 bp Alu repeat sequence polymorhism of angiotensin I converting enzyme, and paraoxonase Gln192Arg PON1 polymorphisms) with the presence and extent of early onset CAD.
  
  
  METHODS
  DNA was isolated and amplified from 90 consecutive patients with angiographically proven early onset CAD (ages 41 ± 5 for men, 49 ± 7 for women) and also from 90 control subjects with no significant coronary obstruction angiographically (ages 42 ± 5 for men, 48 ± 6 for women). Multifactor dimensionality reduction (MDR) analysis was performed to identify a model of CAD based on both genetic and conventional risk factors.
  
  
  RESULTS
  MDR analysis detected a significant model with four genes (prediction success ∼ 61%, p = 0.03). When the total number of the conventional risk factors is analysed with the candidate polymorphisms, a different model is identified that includes three of the four genes from the above model and achieves a similar prediction of CAD as the gene only model.
  
  
  CONCLUSIONS
  These data indicate that gene-gene and gene-environmental risk interactions form significant models in predicting early onset CAD.
authors: Department of Cardiology, Faculty of Medicine, Marmara University, Istanbul, Turkey. magirbasli@gmail.com
authors: M
authors: M
authors: Agirbasli
authors: A I
authors: AI
authors: Guney
authors: H S
authors: HS
authors: Ozturhan
authors: D
authors: D
authors: Agirbasli
authors: K
authors: K
authors: Ulucan
authors: D
authors: D
authors: Sevinc
authors: D
authors: D
authors: Kirac
authors: K K
authors: KK
authors: Ryckman
authors: S M
authors: SM
authors: Williams
mesh_terms: D000328:Adult; D017668:Age of Onset; D043303:Aryldialkylphosphatase / Q000235:genetics*; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D058011:Multifactor Dimensionality Reduction; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D014421:Turkey / Q000453:epidemiology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A