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

Abstract

Objectives: 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. Methods: Genotyping of these polymorphisms was performed using polymerase chain reaction with confronting two-pair primers assay. Results: 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. Conclusions: SIRT 1 polymorphisms, rs7069102 and rs2273773, are associated with abnormal cholesterol metabolism and coronary artery calcification, respectively, in Japanese HD patients, especially in males. © 2012 National Kidney Foundation, Inc.