SIRT1 gene polymorphisms are associated with nondiabetic type 1 cardiorenal syndrome

Ann Hum Genet. 2019 Nov;83(6):445-453. doi: 10.1111/ahg.12338. Epub 2019 Jul 29.

Abstract

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.

Keywords: SIRT1; acute kidney injury; cardiorenal syndrome; single-nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cardio-Renal Syndrome / diagnosis*
  • Cardio-Renal Syndrome / genetics*
  • Case-Control Studies
  • Genetic Association Studies* / methods
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Sirtuin 1 / genetics*

Substances

  • SIRT1 protein, human
  • Sirtuin 1