2015-02-01, IZMIRLI, Muzeyyen, GOKTEKIN, Omer, Bacaksiz, AHMET, Uysal, Omer, Kilic, Ulkan, BACAKSIZ, AHMET, UYSAL, ÖMER

Objective: Cardiovascular disease (CVD) is the leading cause of death in Europe. One of the candidate molecule affecting epigenetic mechanisms of CVD is the SIRT1, a subclass of sirtuins, is located on the long arm of chromosome 10 (10q21.3). Particularly, the relation between 2827 A>G polymorphism of the SIRT1 positioned on exon 2, leading to conversion of histidine to arginine, and the formation of CVD is not known yet. One of the activator of SIRT1, resveratrol, is also known as a cardioprotective molecule. On the other hand, the parameters including exercise, occupation and age affect CVD. The aim of the present study was to investigate the effect of the rs144124002 (2827 A>G) single nucleotide polymorphisms (SNP) of SIRT1 and exercise-occupation-age parameters on CVD. Methods: SNP of SIRT1 were analyzed using DNA isolation, the polymerase chain reaction (PCR) and restriction fragment length polymorphism. To do so, large cohorts of CVD patients (n=293) and healthy controls (n=117) who directed Cardiology Department of Bezmialem Vakıf University, Bezmialem Vakıf University Hospital were used. Results: In this study, when we assessed CVD and control groups about 2827 A>G polymorphism, all individuals were determined as homozygous genotype. We found a positive effect between the modifications of resveratrol, exercise, age and occupation and CVD (OR=0.17; CI 95%, 0.1-0.2; p≤0.001). Conclusion: This is the first study demonstrating the correlation between the SIRT1 rs144124002 polymorphism and CVD in Turkish population. (Anatolian J Cardiol 2015; 15: 103-6) Key words: SIRT1, resveratrol, epigenetic, polymorphism, cardiovascular disease

2014-02-28, KILIC, Ulkan, GOK, Ozlem, Bacaksiz, AHMET, IZMIRLI, Muzeyyen, Elibol-Can, BİRSEN, Uysal, Omer, BACAKSIZ, AHMET, ELİBOL, BİRSEN, UYSAL, ÖMER

Cardiovascular disease (CVD), the leading cause of death worldwide, is related to gene-environment interactions due to epigenetic factors. SIRT1 protein and its downstream pathways are critical for both normal homeostasis and protection from CVD-induced defects. The aim of this study was to investigate the association between SIRT1 single nucleotide polymorphisms (SNPs) (rs7895833 A.G in the promoter region, rs7069102 C.G in intron 4 and rs2273773 C.T in exon 5 silent mutation) and SIRT1 and eNOS (endothelial nitric oxide synthase) protein expression as well as total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) in CVD patients as compared to controls. The frequencies of mutant genotypes and alleles for rs7069102 and rs2273773 were significantly higher in patients with CVD compared to control group. The risk for CVD was increased by 2.4 times for rs7069102 and 1.9 times for rs2273773 in carriers of mutant allele compared with carriers of wild-type allele pointing the protective role of C allele for both SNPs against CVD. For rs7895833, there was no significant difference in genotype and allele distributions between groups. SIRT1 protein, TAS, TOS and OSI levels significantly increased in patients as compared to control group. In contrast, level of eNOS protein was considerably low in the CVD patients. An increase in the SIRT1 expression in the CVD patients carrying mutant genotype for rs7069102 and heterozygote genotype for all three SNPs was observed. This is the first study reporting an association between SIRT1 gene polymorphisms and the levels of SIRT1 and eNOS expressions as well as TAS, TOS and OSI