Association of the CYBA, PPARGC1A, PPARG3, and PPARD gene variants with coronary artery disease and metabolic risk factors of coronary atherosclerosis in a Russian population.
Abnormalities in lipid metabolism and enhanced oxidative stress are considered as major risk factors for coronary atherosclerosis. Functional genetic variations in genes whose products are involved in lipid metabolism and antioxidant defense could therefore modulate risk of coronary artery disease (CAD). In this study, we evaluate whether the PPARGC1A Gly482Ser, PPARG3 (-681)C/G, PPARD +294T/C, and CYBA +242C/T gene variants confer the risk of CAD in a Russian population. A total of 313 CAD patients and 132 controls with no clinical sign of CAD were studied. The polymorphic markers were tested using a TaqMan assay. Allele and genotype frequencies in CAD patients and controls were compared using the Yates chi(2) test. Association of the genetic markers with metabolic risk factors of arterial atherosclerosis was studied using the analysis of variance test and then adjusted for conventional risk factors in the multiple regression analysis. For CYBA +242C/T, both the allele T and genotype T/T showed significant association with higher risk of CAD (odds ratio =1.49 and 3.89, respectively). The allele C and genotype C/C of the +294T/C marker of PPARD were associated with increased risk of CAD providing an odds ratio of 2.12 and 2.78, respectively. The risk variants of CYBA +242C/T and PPARD +294T/C markers were associated with higher low-density lipoprotein cholesterol and increased total serum cholesterol, respectively. In conclusion, the CYBA +242C/T and PPARD +294T/C variants modulate risk of CAD through their associations with atherogenic serum lipid profiles.
Department of Molecular Diagnostics, National Research Center GosNIIgenetika, 1st Dorozhny proezd 1, 117545 Moscow, Russia.
Alexey G
AG
Nikitin
Dimitry A
DA
Chistiakov
Larissa O
LO
Minushkina
Dmitry A
DA
Zateyshchikov
Valery V
VV
Nosikov
D000368:Aged; D001794:Blood Pressure / Q000235:genetics; D015992:Body Mass Index; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008055:Lipids / Q000097:blood; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D016017:Odds Ratio; D047494:PPAR delta / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D012426:Russia; D014157:Transcription Factors / Q000235:genetics*
D006360:Heat-Shock Proteins; D008055:Lipids; D047494:PPAR delta; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D019255:NADPH Oxidases; C086986:CYBA protein, human