title: SIRT1 gene polymorphisms affect the protein expression in cardiovascular diseases.
abstract: 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.
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
authors.forename: Ulkan
authors.initials: U
authors.lastname: Kilic
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Gok
authors.affiliation: Department of Cardiology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Bacaksiz
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey ; Department of Medical Biology, Faculty of Medicine, Mustafa Kemal University, Hatay, Turkey.
authors.forename: Muzeyyen
authors.initials: M
authors.lastname: Izmirli
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
authors.forename: Birsen
authors.initials: B
authors.lastname: Elibol-Can
authors.affiliation: Department of Biostatistics, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
authors.forename: Omer
authors.initials: O
authors.lastname: Uysal
mesh_terms: D000368:Aged; D000483:Alleles; D000975:Antioxidants / Q000378:metabolism; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005091:Exons; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D056564:Sirtuin 1 / Q000235:genetics*
chemical_list: D000975:Antioxidants; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C447939:SIRT1 protein, human; D056564:Sirtuin 1