Energy Homeostasis Gene Nucleotide Variants and Survival of Hemodialysis Patients—A Genetic Cohort Study

Abstract

Background: Patients undergoing hemodialysis (HD) therapy have an increased risk of death compared to the general population. We investigated whether selected single nucleotide variants (SNVs) involved in glucose and lipid metabolism are associated with mortality risk in HD patients. Methods: The study included 805 HD patients tested for 11 SNVs in FOXO3, IGFBP3, FABP1, PCSK9, ANGPTL6, and DOCK6 using HRM analysis and TaqMan assays. FOXO3, IGFBP3, L-FABP, PCSK9, ANGPTL6, and ANGPTL8 plasma concentrations were measured by ELISA in 86 individuals. The Kaplan–Meier method and Cox proportional hazards models were used for survival analyses. Results: We found out that the carriers of a C allele in ANGPTL6 rs8112063 had an increased risk of all-cause, cardiovascular, and cardiac mortality. In addition, the C allele of DOCK6 rs737337 was associated with all-cause and cardiac mortality. The G allele of DOCK6 rs17699089 was correlated with the mortality risk of patients initiating HD therapy. The T allele of FOXO3 rs4946936 was negatively associated with cardiac and cardiovascular mortality in HD patients. We observed no association between the tested proteins’ circulating levels and the survival of HD patients. Conclusions: The ANGPTL6 rs8112063, FOXO3 rs4946936, DOCK6 rs737337, and rs17699089 nucleotide variants are predictors of survival in patients undergoing HD.

Correlations of PCSK9 and LDLR Gene Polymorphisms and Serum PCSK9 Levels With Atherosclerosis and Lipid Metabolism in Patients on Maintenance Hemodialysis

“…Patients on HD present a dramatic increase in cardiovascular death and mortality 22 . Patients undergoing HD therapy possess an elevated risk of mortality in comparison with the general population 23 . In spite of great achievements in technology that one would expect to improve the survival of patients, mortality and morbidity in patients with HD remain high 24 .…”

“…22 Patients undergoing HD therapy possess an elevated risk of mortality in comparison with the general population. 23 In spite of great achievements in technology that one would expect to improve the survival of patients, mortality and morbidity in patients with HD remain high. 24 This study focused on the relations between PCSK9 and LDLR gene polymorphisms as well as serum PCSK9 levels and atherosclerosis with lipid metabolism in patients on maintenance HD.…”