SIRTUIN 1 Gene Polymorphisms are Associated With Cholesterol Metabolism and Coronary Artery Calcification in Japanese Hemodialysis Patients

Department of Advanced Medicine for Uremia, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan.
Journal of Renal Nutrition (Impact Factor: 1.87). 01/2012; 22(1):114-9. DOI: 10.1053/j.jrn.2011.10.025
Source: PubMed


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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    • "SIRT1 is mapped on chromosome 10 (10q21.3) and polymorphic variants of this gene have been studied in the susceptibility of several disorders, such as CVD [12], Type 2 diabetes (T2D) [13] [14], glucose tolerance [15], overweight [16], lipid profiles and coronary artery [17], body fat and blood pressure [18], carotid plaque [19] and aging [20]. Promoter region variants may account for differential SIRT1 expression, rendering individuals susceptible to certain pathologies. "
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    ABSTRACT: Background: Sirtuins (SIRT) have recently been identified as the pivotal regulators of lifespan and health. SIRT1 has protective effects against cardiovascular disease (CVD) and through its deacetylase activity it regulates numerous essential pathways including regulating blood pressure, reducing atherosclerosis, heart protection against oxidative stress and inducing cardiac cell survival and growth. Aims: Therefore, this study was conducted to evaluate whether two genetic polymorphisms of SIRT1 rs3758391 T/C and rs369274325 G/T are associated with the risk of CVD. Material and methods: A total of 500 Iranian subjects including 250 CVD patients and 250 healthy individuals as the control group were recruited in this case-control study. Genotyping of SIRT1 rs3758391 T/C and rs369274325 G/T polymorphisms were performed using PCR-RFLP and Tetra-ARMS PCR methods, respectively. Results: Our findings indicated a significant difference between two groups regarding the SIRT1 rs3758391 CC genotype in both additive and recessive models. The rs3758391 CC genotype was found to be more frequent in CVD patients than in the controls (19% vs. 6%), suggesting a statistically significant difference in either of additive (CC vs. TT; OR = 3.06, P = 0.001) as well as recessive models (CC vs. TT. +. CT genotype; OR = 3.72, P = 0.001). Conclusion: Our study for the first time suggests that the SIRT1 rs3758391 T/C polymorphism may confer an increased risk of CVD in both additive and recessive models, in this Iranian population.
    Egyptian Journal of Medical Human Genetics 01/2015; 4(2). DOI:10.1016/j.ejmhg.2014.11.005
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    • "Genetic variants of the SIRT1 gene have been shown to be associated with human diabetes and obesity-related phenotypes in several previous studies [20-22], while only a few genetic association studies for the SIRT1 gene and lipid metabolism have been reported [23]. Almost all genetic variants detected in the SIRT1 gene were synonymous, only a few variants with possible functional changes were reported in the promoter region [24]. "
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    ABSTRACT: Background Dyslipidemia due to high total cholesterol, LDL-cholesterol, triglycerides, or low HDL-cholesterol is an important risk factor for coronary heart disease (CHD). Both SIRT1 and PUFAs can influence the expression of genes for nuclear receptors and transcription factors related to lipid metabolism such as LXRα, LXRβ, PPARα, SREBP-1c. Methods A total of 707 Japanese males and 723 females were randomly selected from the participants who visited a medical center for routine medical check-ups. We analyzed the combined effects of the genotype/haplotype of the SIRT1 gene and dietary n-6/n-3 PUFA intake ratio on the determination of serum lipid levels. Results We found that the SIRT1 gene marked with haplotype 2 was associated with decreased serum LDL-cholesterol and increased HDL-cholesterol levels. In addition, the associations between the SIRT1 haplotype 2 and decreased LDL-C and increased HDL-C levels were only observed in the low n-6/n-3 PUFA intake ratio group, but not in the high n-6/n-3 PUFA intake ratio group. Conclusions Our findings indicate that the combination of genetic variation in the SIRT1 gene and dietary n-6 and/or n-3 PUFA intake influence the determination of inter-individual variations of serum levels of LDL-C and HDL-C.
    Lipids in Health and Disease 01/2013; 12(1):4. DOI:10.1186/1476-511X-12-4 · 2.22 Impact Factor
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    • "An increased risk of large artery atherosclerotic stroke has been shown in a Chinese population of cigarette smokers carrying polymorphisms in several DNA repair genes [65]. In a recent study, an association between a SIRT1 gene polymorphism and cholesterol metabolism and coronary artery calcification in hemodialysis patients has been observed [66]. The authors suggest that SIRT1 polymorphism may be associated with development of cardiovascular disease in hemodialysis patients. "
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    ABSTRACT: Atherosclerosis is the leading cause of morbidity and mortality among Western populations. Over the past two decades, considerable evidence has supported a crucial role for DNA damage in the development and progression of atherosclerosis. These findings support the concept that the prolonged exposure to risk factors (e.g., dyslipidemia, smoking and diabetes mellitus) leading to reactive oxygen species are major stimuli for DNA damage within the plaque. Genomic instability at the cellular level can directly affect vascular function, leading to cell cycle arrest, apoptosis and premature vascular senescence. The purpose of this paper is to review current knowledge on the role of DNA damage and DNA repair systems in atherosclerosis, as well as to discuss the cellular response to DNA damage in order to shed light on possible strategies for prevention and treatment.
    International Journal of Molecular Sciences 12/2012; 13(12):16929-44. DOI:10.3390/ijms131216929 · 2.86 Impact Factor
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