SIRT1 gene polymorphisms affect the protein expression in cardiovascular diseases

• Published in: PloS one Vol. 9; no. 2; p. e90428
• Main Authors: Kilic, Ulkan, Gok, Ozlem, Bacaksiz, Ahmet, Izmirli, Muzeyyen, Elibol-Can, Birsen, Uysal, Omer
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-02-2014; Public Library of Science (PLoS)
• Subjects: Aged; Alleles; Antioxidants; Antioxidants (Nutrients); Antioxidants - metabolism; Biology; Cardiovascular diseases; Carriers; Case-Control Studies; Coronary Artery Disease - genetics; Coronary Artery Disease - metabolism; Coronary Artery Disease - pathology; Defects; Endothelium; Epigenetic inheritance; Epigenetics; Exons; Female; Gene expression; Gene mutation; Gene-Environment Interaction; Genes; Genetic aspects; Genetic Predisposition to Disease; Genotypes; Heterozygotes; Homeostasis; Humans; Introns; Kinases; Male; Medicine; Middle Aged; Mutation; Nitric oxide; Nitric Oxide Synthase Type III - genetics; Nitric-oxide synthase; Oxidative Stress; Patients; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Risk management; Rodents; Single nucleotide polymorphisms; Single-nucleotide polymorphism; SIRT1 protein; Sirtuin 1 - genetics; Istanbul Turkey; Turkey
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0090428

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.