Heme oxygenase-1 repeat polymorphism in septic acute kidney injury

PLoS One. 2019 May 23;14(5):e0217291. doi: 10.1371/journal.pone.0217291. eCollection 2019.

Abstract

Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter study was part of the national FINNAKI study. We genotyped 300 patients with severe AKI (KDIGO 2 or 3) and 353 controls without AKI (KDIGO 0) for the guanine-thymine (GTn) repeat in the promoter region of the HMOX1 gene. The allele calling was based on the number of repeats, the cut off being 27 repeats in the S-L (short to long) classification, and 27 and 34 repeats for the S-M-L2 (short to medium to very long) classification. The plasma concentrations of heme oxygenase-1 (HO-1) enzyme were measured on admission. The allele distribution in our patients was similar to that published previously, with peaks at 23 and 30 repeats. The S-allele increases AKI risk. An adjusted OR was 1.30 for each S-allele in an additive genetic model (95% CI 1.01-1.66; p = 0.041). Alleles with a repeat number greater than 34 were significantly associated with lower HO-1 concentration (p<0.001). In septic patients, we report an association between a short repeat in HMOX1 and AKI risk.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / enzymology
  • Acute Kidney Injury / epidemiology
  • Acute Kidney Injury / genetics*
  • Aged
  • Alleles
  • Cohort Studies
  • Comorbidity
  • Critical Illness
  • Female
  • Finland / epidemiology
  • Genetic Predisposition to Disease
  • Genotype
  • Heme Oxygenase-1 / blood
  • Heme Oxygenase-1 / genetics*
  • Humans
  • Male
  • Middle Aged
  • Minisatellite Repeats*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • Prospective Studies
  • Risk Factors
  • Sepsis / enzymology
  • Sepsis / epidemiology
  • Sepsis / genetics*

Substances

  • HMOX1 protein, human
  • Heme Oxygenase-1

Grants and funding

This study received grants from Munuaissäätiö fund (https://www.muma.fi/liitto/munuaissaatio)(LV), and The Finnish Society of Anaesthesiologists (https://www.say.fi/fi/)(LV). In addition, funding by grants TYH 2013343, 2016243, 2017241, and Y102011091 from the Helsinki University Hospital research funding (http://www.hus.fi/en/researchers/Pages/default.aspx)(VP), and a grant from the Sigrid Juselius Foundation (https://sigridjuselius.fi/en/)(VP) were received. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.