SIRTUIN 1 gene polymorphisms are associated with cholesterol metabolism and coronary artery calcification in Japanese hemodialysis patients.
ABSTRACT Sirtuin 1 (SIRT1), a longevity gene, protects cells against oxidative and genotoxic stress. This study aimed to investigate the association of SIRT 1 gene single-nucleotide polymorphisms, namely, rs7895833, rs7069102, and rs2273773 with lipid profiles and coronary artery calcification score in 219 Japanese hemodialysis (HD) patients.
Genotyping of these polymorphisms was performed using polymerase chain reaction with confronting two-pair primers assay.
The A allele frequency of rs7895833 and G allele frequency of rs7069102 were significantly lower in HD patients (0.228 and 0.131, respectively) than those in 803 control subjects (general population) (0.289 and 0.181, respectively) (P = .010 and P = .012, respectively). However, the allele frequency of rs2273773 was not significantly different from that in the control subjects. Multivariate analysis adjusted for age and duration on HD demonstrated that the serum levels of total and low-density lipoprotein cholesterol were significantly high in G allele carriers of rs7069102 compared with CC genotype in male HD patients. Coronary artery calcification score was significantly high in C allele carriers of rs2273773 in all and male HD patients.
SIRT 1 polymorphisms, rs7069102 and rs2273773, are associated with abnormal cholesterol metabolism and coronary artery calcification, respectively, in Japanese HD patients, especially in males.
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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.PLoS ONE 02/2014; 9(2):e90428. · 3.53 Impact Factor
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ABSTRACT: 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.Anadolu kardiyoloji dergisi: AKD = the Anatolian journal of cardiology 04/2014; · 0.76 Impact Factor
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ABSTRACT: Obesity, especially at mid-life, is a major risk factor for atherosclerosis, insulin resistance and the metabolic syndrome, which in turn contrib-ute to coronary artery disease (CAD), Type 2 diabetes and Alzheimer's disease (AD). The rise in overweight and obesity in all societies is prompting intense research into the causes and effects of the condition. Obesity disrupts many body systems including glucose and lipid me-tabolism, circadian rhythms and liver function. It also causes or increases inflammation and oxi-dative stress. Within cells, the endoplasmic re-ticulum (ER) appears to be particularly suscep-tible to such metabolic disruption. Sirtuin 1 (Sirt1) and leptin have received attention recently as they are central regulatory factors for the body's metabolic pathways which interact at particular levels, for example lipid and Abeta metabolism. This mini-review discusses recent findings con-cerning obesity, lipid metabolism and the role of Sirtuin 1 and how all influence the ER. A greater understanding of obesity and its effects on me-tabolic control systems of the body are required, to develop pharmacological, dietary and lifestyle changes that will reduce the incidence of CAD, Type 2 diabetes and AD.