SIRT1 Single Nucleotide Polymorphisms Research Articles

Diet and SIRT1 Genotype Interact to Modulate Aging-Related Processes in Patients with Coronary Heart Disease: From the CORDIOPREV Study.

We investigated whether long-term consumption of two healthy diets (low-fat (LF) or Mediterranean (Med)) interacts with SIRT1 genotypes to modulate aging-related processes such as leucocyte telomere length (LTL), oxidative stress (OxS) and inflammation in patients with coronary heart disease (CHD). LTL, inflammation, OxS markers (at baseline and after 4 years of follow-up) and SIRT1-Single Nucleotide Polymorphisms (SNPs) (rs7069102 and rs1885472) were determined in patients from the CORDIOPREV study. We analyzed the genotype-marker interactions and the effect of diet on these interactions. Regardless of the diet, we observed LTL maintenance in GG-carriers for the rs7069102, in contrast to carriers of the minor C allele, where it decreased after follow-up (p = 0.001). The GG-carriers showed an increase in reduced/oxidized glutathione (GSH/GSSG) ratio (p = 0.003), lower lipid peroxidation products (LPO) levels (p < 0.001) and a greater decrease in tumor necrosis factor-alpha (TNF-α) levels (p < 0.001) after follow-up. After the LF diet intervention, the GG-carriers showed stabilization in LTL which was significant compared to the C allele subjects (p = 0.037), although the protective effects found for inflammation and OxS markers remained significant after follow-up with the two diets. Patients who are homozygous for the SIRT1-SNP rs7069102 (the most common genotype) may benefit from healthy diets, as suggested by improvements in OxS and inflammation in patients with CHD, which may indicate the slowing-down of the aging process and its related diseases.

Determination of a possible relationship between a single nucleotide polymorphism (SNP) in the promoter region of the SIRT1 gene and production and reproduction traits in the Agerolese cattle breed.

Sirtuins (sir2-like proteins) belong to the family of class III NAD-dependent histone deacetylases. Among them, SIRT1 is the most studied sirtuin. It plays a key role in many biological processes in the liver, adipose tissue, muscle, pancreas, testis, ovary and mammary gland. It has an important function in endocrine signaling, with a specific role in glucose and fat metabolism. To date, in bovine species, only few SIRT1 single nucleotide polymorphisms (SNPs) have been reported in the literature. Thus, the aims of the present study were to estimate the allele and genotype frequencies at the g.-274C G locus in the promoter region of the SIRT1 gene and to investigate, for the first time, the relationship among different genotypes and milk production and some reproduction traits in a sample of cows belonging to the Agerolese breed. All the animals were genotyped at the abovementioned locus using the PCR-RFLP technique. The investigated population was found to be polymorphic at the investigated locus. Concerning milk production performances, significant differences between genotypes were found in daily milk yield (DMY), fat percentage (FC), lactation length (LL), peak daily milk yield (PY) and 305-day milk yield (305MY). Moreover, the effect of the g.-274C G genotype on age at first calving and calving period was significant. In conclusion, our findings are promising and should encourage scientists to further investigate the effect of genetic polymorphism of sirtuins on milk performance and reproductive traits.

Possible association between SIRT1 single nucleotide polymorphisms and predisposition to antisocial personality traits in Chinese adolescents

Accumulating evidence suggests an association between the SIRT1 gene and human psychiatric disorders. The aim of the study was to investigate the association between SIRT1 and predisposition to antisocial personality traits (ASP) in Chinese adolescents. Participants consisted of 327 controls and 261 juvenile offenders who were diagnosed with predisposition to ASP according to the Personality Diagnostic Questionnaire. Four tag single nucleotide polymorphisms (tagSNPs) of SIRT1, namely rs12778366, rs7896005, rs10823112, and rs4746720, were genotyped. Association analysis between individual SNPs and ASP risk revealed the CC genotype of rs4746720 to be significantly associated with reduced risk of ASP (OR = 0.51, 95% CI = 0.33–0.77, adjusted P = 0.007). Haplotype analysis showed the TAAC haplotype was associated with reduced susceptibility to ASP (OR = 0.72, 95% CI = 0.57–0.91, P = 0.005). Moreover, rs4746720 variants were found to not only have a direct impact on ASP susceptibility but also modulate the effect of alcohol consumption (Y = 0.022X + 0.431 vs. Y = −0.066X + 0.387). The present study is the first to report a significant association between SIRT1 polymorphisms and ASP in adolescents. This finding is expected to aid in the development of effective interventions for this socially and personally costly disorder.

SIRT1 Polymorphisms and Serum-Induced SIRT1 Protein Expression in Aging and Frailty: The CHAMP Study.

The nutrient sensing protein, SIRT1 influences aging and nutritional interventions such as caloric restriction in animals, however, the role of SIRT1 in human aging remains unclear. Here, the role of SIRT1 single-nucleotide polymorphisms (SNPs) and serum-induced SIRT1 protein expression (a novel assay that detects circulating factors that influence SIRT1 expression in vitro) were studied in the Concord Health and Ageing in Men Project (CHAMP), a prospective cohort of community dwelling men aged 70 years and older. Serum-induced SIRT1 expression was not associated with age or mortality, however participants within the lowest quintile were less likely to be frail (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.17-0.69, N = 1,309). Serum-induced SIRT1 expression was associated with some markers of body composition and nutrition (height, weight, body fat and lean % mass, albumin, and cholesterol) but not disease. SIRT1 SNPs rs2273773, rs3740051, and rs3758391 showed no association with age, frailty, or mortality but were associated with weight, height, body fat and lean, and albumin levels. There were some weak associations between SIRT1 SNPs and arthritis, heart attack, deafness, and cognitive impairment. There was no association between SIRT1 SNPs and the serum-induced SIRT1 assay. SIRT1 SNPs and serum-induced SIRT1 expression in older men may be more closely associated with nutrition and body composition than aging and age-related conditions.

SIRT1 Gene Polymorphisms Affect the Protein Expression in Cardiovascular Diseases

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.

Sirtuin1 single nucleotide polymorphism (A2191G) is a diagnostic marker for vibration-induced white finger disease

BackgroundVibration-induced white finger disease (VWF), also known as hand-arm vibration syndrome, is a secondary form of Raynaud’s disease, affecting the blood vessels and nerves. So far, little is known about the pathogenesisof the disease. VWF is associated with an episodic reduction in peripheral blood flow. Sirtuin 1, a class III histone deacetylase, has been described to regulate the endothelium dependent vasodilation by targeting endothelial nitric oxide synthase. We assessed Sirt1single nucleotide polymorphisms in patients with VWF to further elucidate the role of sirtuin 1 in the pathogenesis of VWF.MethodsPeripheral blood samples were obtained from 74 patients with VWF (male 93.2%, female 6.8%, median age 53 years) and from 317 healthy volunteers (gender equally distributed, below 30 years of age). Genomic DNA was extracted from peripheral blood mononuclear cells and screened for potential Sirt1single nucleotide polymorphisms. Four putative genetic polymorphisms out of 113 within the Sirt1 genomic region (NCBI Gene Reference: NM_012238.3) were assessed. Allelic discrimination was performed by TaqMan-polymerasechainreaction-based allele-specific genotyping single nucleotide polymorphism assays.ResultsSirt1single nucleotide polymorphism A2191G (Assay C_25611590_10, rs35224060) was identified within Sirt1 exon 9 (amino acid position 731, Ile → Val), with differing allelic frequencies in the VWF population (A/A: 70.5%, A/G: 29.5%, G/G: 0%) and the control population (A/A: 99.7%, A/G: 0.3%, G/G: 0.5%), with significance levels of P < 0.001 (Mann–Whitney U test (two-tailed) P <0.001; F-exact t-test and Chi-square test with Yates correction (all two-tailed): P <0.0001). The heterogeneous A/G genotype in base pair position 2191 is significantly overrepresented in the VWF patient population when compared with healthy controls.ConclusionWe identified theSirt1A2191Gsingle nucleotide polymorphism as a diagnostic marker for VWF.

Variants in the SIRT1 Gene May Affect Diabetes Risk in Interaction With Prenatal Exposure to Famine

OBJECTIVETo investigate whether SIRT1, a nutrient-sensing histone deacetylase, influences fetal programming during malnutrition.RESEARCH DESIGN AND METHODSIn 793 individuals of the Dutch Famine Birth Cohort, we analyzed the interaction between three SIRT1 single nucleotide polymorphisms (SNPs) and prenatal exposure to famine on type 2 diabetes risk.RESULTSIn the total population (exposed and unexposed), SIRT1 variants were not associated with type 2 diabetes. A significant interaction was found between two SIRT1 SNPs and exposure to famine in utero on type 2 diabetes risk (P = 0.03 for rs7895833; P = 0.01 for rs1467568). Minor alleles of these SNPs were associated with a lower prevalence of type 2 diabetes only in individuals who had been exposed to famine prenatally (odds ratio for rs7895833 0.50 [95% CI 0.24–1.03], P = 0.06; for rs1467568 0.48 [0.25–0.91], P = 0.02).CONCLUSIONSSIRT1 may be an important genetic factor involved in fetal programming during malnutrition, influencing type 2 diabetes risk later in life.

Dietary factors and lung function in the general population: wine and resveratrol intake

Wine intake is associated with a better lung function in the general population, yet the source of this effect is unknown. Resveratrol, a polyphenol in wine, has anti-inflammatory properties in the lung, its effects being partially mediated via induction of Sirtuin (SIRT)1 activity. We assessed the impact of wine and resveratrol intake, and SIRT1 single-nucleotide polymorphisms (SNPs) on lung function in the general population. Effects of red and white wine and resveratrol intake on forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC were analysed in the population-based Doetinchem cohort (n=3,224). Associations of four tagging SIRT1 SNPs with lung function were analysed in the Doetinchem (n=1,152) and Vlagtwedde-Vlaardingen (n=1,390) cohorts. Resveratrol intake was associated with higher FVC levels, and white wine intake with higher FEV(1) levels and lower risk of airway obstruction. SIRT1 SNPs were not significantly associated with level or course of lung function, either directly or indirectly via wine or resveratrol intake. This study shows a positive association of resveratrol intake with lung function in the general population, confirms the previously reported positive association of white wine intake with higher levels of FEV(1), and additionally shows an association with a higher FEV(1)/FVC ratio. These effects probably do not run via SNPs in SIRT1.