The role of genetic polymorphisms in KCNN2 in cardiovascular complications in patients with renal failure.

Abstract

Patients with end-stage renal disease (ESRD) are at a higher risk of cardiovascular (CV) complications and mortality compared to the general population. This study aimed to investigate the genetic polymorphisms of KCNN2, a key gene encoding a subtype of small-conductance calcium-activated potassium (SK) channels, which regulate an important SK current pathway potentially involved in the development of CV complications, particularly arrhythmias, in ESRD patients. A total of 169 ESRD patients were enrolled in this study. The patients were divided into two groups based on the presence of CV complications: Group I, consisting of 84 patients without CV complications, and Group II, comprising 85 patients with CV complications. Twelve tagging single nucleotide polymorphisms (tSNPs) in KCNN2 were examined. Polymerase chain reaction (PCR) was performed, and genotyping was correlated with CV complications in each group. The TC and CC genotypes of rs10076582, and the GT and TT genotypes of rs11738819 in the KCNN2 gene, were associated with an increased risk of CV complications in ESRD patients. After adjusting for potential risk factors, these associations remained significant. Additionally, KCNN2 haplotypes with the allele combinations GGCCCTCCGAG and AGTCCTCCGGT were significantly associated with a higher risk of CV complications in ESRD patients. In conclusion, our findings report that specific genetic polymorphisms in the KCNN2 gene, particularly the rs10076582 and rs11738819 variants, as well as GGCCCTCCGAG and AGTCCTCCGGT haplotypes, are significantly associated with an increased risk of cardiovascular complications in ESRD patients. These genetic markers may serve as potential biomarkers for identifying individuals at high risk of cardiovascular complications in this vulnerable population.