University of Oulu

Vilander LM, Vaara ST, Donner KM, Lakkisto P, Kaunisto MA, Pettilä V, et al. (2019) Heme oxygenase-1 repeat polymorphism in septic acute kidney injury. PLoS ONE 14(5): e0217291. https://doi.org/10.1371/journal.pone.0217291

Heme oxygenase-1 repeat polymorphism in septic acute kidney injury

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Author: Vilander, Laura M.1,2; Vaara, Suvi T.1,2; Donner, Kati M.3;
Lakkisto, Paivi2,4,5; Kaunisto, Mari A.3; Pettila, Ville1,2,6; Laru-Sompa, Raili7; Pulkkinen, Anni7; Saarelainen, Minna7; Reilama, Mikko7; Tolmunen, Sinikka7; Rantalainen, Ulla7; Miettinen, Marja7; Suvela, Markku8; Pesola, Katrine8; Saastamoinen, Pekka8; Kauppinen, Sirpa8; Kaukonen, Kirsi-Maija6; Korhonen, Anna-Maija6; Nisula, Sara6; Vaara, Suvi1,2,6; Suojaranta-Ylinen, Raili6; Mildh, Leena6; Haapio, Mikko6; Nurminen, Laura6; Sutinen, Sari6; Pettila, Leena6; Laitinen, Helina6; Syrja, Heidi6; Henttonen, Kirsi6; Lappi, Elina6; Boman, Hillevi6; Varpula, Tero9; Porkka, Paivi9; Sivula, Mirka9; Rahkonen, Mira9; Tsurkka, Anne9; Nieminen, Taina9; Prittinen, Niina9; Alaspaa, Ari10; Salanto, Ville10; Juntunen, Hanna10; Sanisalo, Teija10; Parviainen, Ilkka11; Uusaro, Ari11; Ruokonen, Esko11; Bendel, Stepani11; Rissanen, Niina11; Lang, Maarit11; Rahikainen, Sari11; Rissanen, Saija11; Ahonen, Merja11; Halonen, Elina11; Vaskelainen, Eija11; Poukkanen, Meri12; Lintula, Esa12; Suominen, Sirpa12; Heikkinen, Jorma13; Lavander, Timo13; Heinonen, Kirsi13; Juopperi, Anne-Mari13; Kaminski, Tadeusz14; Gaddnas, Fiia14; Kuusela, Tuija14; Roiko, Jane14; Karlsson, Sari15; Reinikainen, Matti15; Surakka, Tero15; Jyrkonen, Helena15; Eiserbeck, Tanja15; Kallinen, Jaana15; Lund, Vesa16; Tuominen, Paivi16; Perkola, Pauliina16; Tuominen, Riikka16; Hietaranta, Marika16; Johansson, Satu16; Hovilehto, Seppo17; Kirsi, Anne17; Tiainen, Pekka17; Myllarinen, Tuija17; Leino, Pirjo17; Toropainen, Anne17; Kuitunen, Anne18; Leppanen, Ilona18; Levoranta, Markus18; Hoppu, Sanna18; Sauranen, Jukka18; Tenhunen, Jyrki18; Kukkurainen, Atte18; Kortelainen, Samuli18; Varila, Simo18; Inkinen, Outi19; Koivuviita, Niina19; Kotamaki, Jutta19; Laine, Anu19; Ala-Kokko, Tero20; Laurila, Jouko20; Salkio, Sinikka20; Koivisto, Simo-Pekka21; Hautamaki, Raku21; Skinnar, Maria21
Organizations: 1Univ Helsinki, Dept Anesthesiol Intens Care & Pain Med, Div Intens Care Med, Helsinki, Finland.
2Helsinki Univ Hosp, Helsinki, Finland.
3Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
4Univ Helsinki, Dept Clin Chem, Helsinki, Finland.
5Minerva Fdn, Helsinki, Finland.
6Univ Helsinki, Cent Hosp, Helsinki, Finland.
7Cent Finland Cent Hosp, Jyvaskyla, Finland.
8East Savo Cent Hosp, Savonlinna, Finland.
9Jorvi Cent Hosp, Espoo, Finland.
10KantaHame Cent Hosp, Hameenlinna, Finland.
11Kuopio Univ Hosp, Kuopio, Finland.
12Lapland Cent Hosp, Rovaniemi, Finland.
13Lansi Pohja Cent Hosp, Kemi, Finland.
14Middle Ostrobothnia Cent Hosp, Soite, Finland.
15North Karelia Cent Hosp, Joensuu, Finland.
16Satakunta Hosp Dist, Pori, Finland.
17South Karelia Cent Hosp, Lappeenranta, Finland.
18Tampere Univ Hosp, Tampere, Finland.
19Turku Univ Hosp, Turku, Finland.
20Oulu Univ Hosp, Oulu, Finland.
21Vaasa Cent Hosp, Vaasa, Finland.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.3 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2020042822774
Language: English
Published: Public Library of Science, 2019
Publish Date: 2020-04-28
Description:

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.

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Series: PLoS one
ISSN: 1932-6203
ISSN-E: 1932-6203
ISSN-L: 1932-6203
Volume: 14
Issue: 5
Article number: e0217291
DOI: 10.1371/journal.pone.0217291
OADOI: https://oadoi.org/10.1371/journal.pone.0217291
Type of Publication: A1 Journal article – refereed
Field of Science: 3126 Surgery, anesthesiology, intensive care, radiology
Subjects:
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.
Copyright information: © 2019 Vilander et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
  https://creativecommons.org/licenses/by/4.0/