Research Article: Heme oxygenase-1 repeat polymorphism in septic acute kidney injury

Date Published: May 23, 2019

Publisher: Public Library of Science

Author(s): Laura M. Vilander, Suvi T. Vaara, Kati M. Donner, Päivi Lakkisto, Mari A. Kaunisto, Ville Pettilä, Shree Ram Singh.

http://doi.org/10.1371/journal.pone.0217291

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.

Partial Text

Acute kidney injury (AKI) is a multifactorial syndrome that frequently accompanies critical illness. In a Finnish intensive-care-unit (ICU) cohort, the incidence of AKI was 39% [1]. Clinical risk factors alone fail to reliably predict the development and severity of AKI. Therefore, common genetic variants, genetic polymorphisms, have been studied in association with development and outcome of AKI, but no conclusive evidence about the role of polymorphisms exists.

Altogether 653 patients with sepsis were successfully genotyped for HMOX1-promoter polymorphism. Their demographic and clinical data are presented in Table 1. Of these patients, 300 had KDIGO stage 2 or 3 AKI and 353 did not have AKI (KDIGO stage 0) (Fig 1). Patients with KDIGO stage 1 (N = 189) AKI were not included in the analyses.

In critically ill septic patients we report that the S-allele (<27 repeats) in the HMOX1 promoter region is associated with development of AKI. This finding is in contrast with that previously reported for cardiac-surgery related AKI [5]. The longest repeats (>34) were significantly associated with lower HO-1 concentrations.

 

Source:

http://doi.org/10.1371/journal.pone.0217291

 

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