Hou Jiebin, Xie Xinyue, Tu Qingxian, Li Jie, Ding Jiarong, Shao Guojian, Jiang Qianfeng, Yuan Li, Lai Xueli
Department of Nephrology, the Second Medical Centre, Chinese PLA (People's Liberation Army) General Hospital, Beijing, China.
Division of Nephrology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Ann Hum Genet. 2019 Nov;83(6):445-453. doi: 10.1111/ahg.12338. Epub 2019 Jul 29.
Type 1 cardiorenal syndrome (CRS1) is characterized by acute cardiac disease (e.g., acute heart failure [AHF]), leading to acute kidney injury. Sirtuin 1 (SIRT1), an NAD -dependent deacylase, has been found to be associated with CRS1. To confirm whether a correlation exists between SIRT1 variants and the risk of CRS1, the association between the prevalence of CRS1 and single-nucleotide polymorphisms (SNPs) within the SIRT1 gene was investigated in AHF patients. A total of 316 Chinese AHF participants (158 patients with CRS1 and 158 age- and sex-matched controls) were recruited for the present observational study to investigate the association between nine common SIRT1 SNPs (i.e., rs7895833 G > A, rs10509291 T > A, rs3740051 A > G, rs932658 A > C, rs33957861 C > T, rs7069102 C > G, rs2273773 T > C, rs3818292 A > G, and rs1467568 A > G) and the susceptibility to CRS1. Significant differences in genotype distribution between the control and CRS1 groups were found for rs7895833 and rs1467568. After applying a Bonferroni adjustment, the A allele of rs7895833 was still found to be protective (p = 0.001; odds ratio [OR] = 0.77) against CRS1 in this study population. The AA genotype of rs7895833 and the GA genotype of rs1467568 were associated with a significantly reduced risk of CRS1 (OR = 0.23 and 0.49, respectively). rs7895833 and rs1467568 were further analyzed as a haplotype, and the GA haplotype (rs7895833-rs1467568) exhibited a significant association with CRS1 (p = 0.008), while the AA haplotype showed a significant protective effect (p = 0.022). Our study showed that SIRT1 rs7895833 and rs1467568 polymorphisms had a significant effect on the risk of developing CRS1 in a population in China.
1型心肾综合征(CRS1)的特征是急性心脏疾病(如急性心力衰竭[AHF])导致急性肾损伤。沉默调节蛋白1(SIRT1)是一种依赖烟酰胺腺嘌呤二核苷酸的去乙酰化酶,已发现其与CRS1有关。为了证实SIRT1基因变异与CRS1风险之间是否存在关联,研究了AHF患者中CRS1患病率与SIRT1基因内单核苷酸多态性(SNP)之间的关联。本观察性研究共招募了316名中国AHF参与者(158例CRS1患者和158例年龄及性别匹配的对照),以研究9种常见的SIRT1 SNP(即rs7895833 G>A、rs10509291 T>A、rs3740051 A>G、rs932658 A>C、rs33957861 C>T、rs7069102 C>G、rs2273773 T>C、rs3818292 A>G和rs1467568 A>G)与CRS1易感性之间的关系。发现rs7895833和rs1467568在对照组和CRS1组之间的基因型分布存在显著差异。在应用Bonferroni校正后,本研究人群中仍发现rs7895833的A等位基因对CRS1具有保护作用(p=0.001;优势比[OR]=0.77)。rs7895833的AA基因型和rs1467568的GA基因型与CRS1风险显著降低相关(OR分别为0.23和0.49)。将rs7895833和rs1467568作为单倍型进一步分析,GA单倍型(rs7895833-rs1467568)与CRS1显著相关(p=0.008),而AA单倍型显示出显著的保护作用(p=0.022)。我们的研究表明,SIRT1 rs7895833和rs1467568多态性对中国人群发生CRS1的风险有显著影响。