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

Abstract

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.

Positive association between PPARD rs2016520 polymorphism and coronary heart disease in a Han Chinese population

“…PPARD rs2016520 showed no association with CHD, but was significantly associated with cholesterol metabolism in a Scottish study (Skogsberg et al, 2003). The PPARD rs2016520 polymorphism was associated with serum lipid levels and the risk of CHD in Russians (Nikitin et al, 2010). PPARD rs2016520 increased the effect of low-density lipoprotein-cholesterol on the pathogenesis of CHD in a Turkish population (Yilmaz-Aydogan et al, 2012).…”

“…A number of case-control studies have indicated that PPARD rs2016520 is associated with CHD. A previous study in Russians found a significant association between the PPARD rs2016520 polymorphism and the risk of CHD by modulating lipid levels (Nikitin et al, 2010). A study performed in Tunisians indicated that the minor allele of PPARD rs2016520 was associated with CHD (Jguirim-Souissi et al, 2010;Chehaibi et al, 2013).…”

“…The PPARD protein is highly expressed in the myocardium and is an important transcription factor regulating lipid and glucose metabolism (Skogsberg et al, 2003;Nikitin et al, 2010;Jguirim-Souissi et al, 2010;Yilmaz-Aydogan et al, 2012). In the present study, we investigated the relationship between the PPARD rs2016520 polymorphism and CHD in Han Chinese.…”

“…In previous studies in Russian (Nikitin et al, 2010), Tunisian (Jguirim-Souissi et al, 2010;Chehaibi et al, 2013), Scotsmen (Skogsberg et al, 2003), and Turkish (YilmazAydogan et al, 2012) populations, the G-allele was consistently observed to be a risk factor of CHD. However, we found that the G-allele was a protective factor in the development of CHD in Han Chinese.…”

Study on the Effects of PPARG and PPAR-B/D Gene Variations on Serum LDL Subfractions in Patients with Coronary Heart Disease

“…27,28 PPAR-B/D geni 5'-UTR bölgesinde tanımlanan +294T/C tek nükleotit polimorfizmi (SNP) (rs52016520) minör C alleli ile yüksek LDL kolesterol (LDL-K) ve apoB düzeyleri, vücut kitlesi ve düşük HDL kolesterol (HDL-K) düzeyleri ilişkili olarak aterojenik etkili bulunmuştur. 13,[29][30][31][32][33] Ancak bazı çalışma sonuçları çelişkilidir. [34][35][36] PPAR-B/D +294T/C minör C allelinin yüksek HDL-K düzey-leri ile ilişkili olduğunu ya da serum lipid düzeyle-rine etkisiz olduğunu öne süren çalışmalar da mevcuttur.…”