A1 Refereed original research article in a scientific journal
Heme oxygenase-1 repeat polymorphism in septic acute kidney injury
Authors: Laura M. Vilander, Suvi T. Vaara, Kati M. Donner, Päivi Lakkisto, Mari A. Kaunisto, Ville Pettilä, Raili Laru–Sompa, Anni Pulkkinen, Minna Saarelainen, Mikko Reilama, Sinikka Tolmunen, Ulla Rantalainen, Marja Miettinen, Markku Suvela, Katrine Pesola, Pekka Saastamoinen, Sirpa Kauppinen, Ville Pettilä, Kirsi–Maija Kaukonen, Anna–Maija Korhonen, Sara Nisula, Suvi Vaara, Raili Suojaranta–Ylinen, Leena Mildh, Mikko Haapio, Laura Nurminen, Sari Sutinen, Leena Pettilä, Helinä Laitinen, Heidi Syrjä, Kirsi Henttonen, Elina Lappi, Hillevi Boman, Tero Varpula, Päivi Porkka, Mirka Sivula, Mira Rahkonen, Anne Tsurkka, Taina Nieminen, Niina Prittinen, Ari Alaspää, Ville Salanto, Hanna Juntunen, Teija Sanisalo, Ilkka Parviainen, Ari Uusaro, Esko Ruokonen, Stepani Bendel, Niina Rissanen, Maarit Lång, Sari Rahikainen, Saija Rissanen, Merja Ahonen, Elina Halonen, Eija Vaskelainen, Meri Poukkanen, Esa Lintula, Sirpa Suominen, Jorma Heikkinen, Timo Lavander, Kirsi Heinonen, Anne–Mari Juopperi, Tadeusz Kaminski, Fiia Gäddnäs, Tuija Kuusela, Jane Roiko, Sari Karlsson, Matti Reinikainen, Tero Surakka, Helena Jyrkönen, Tanja Eiserbeck, Jaana Kallinen, Vesa Lund, Päivi Tuominen, Pauliina Perkola, Riikka Tuominen, Marika Hietaranta, Satu Johansson, Seppo Hovilehto, Anne Kirsi, Pekka Tiainen, Tuija Myllärinen, Pirjo Leino, Anne Toropainen, Anne Kuitunen, Ilona Leppänen, Markus Levoranta, Sanna Hoppu, Jukka Sauranen, Jyrki Tenhunen, Atte Kukkurainen, Samuli Kortelainen, Simo Varila, Outi Inkinen, Niina Koivuviita, Jutta Kotamäki, Anu Laine, Tero Ala–Kokko, Jouko Laurila, Sinikka Sälkiö, Simo–Pekka Koivisto, Raku Hautamäki, Maria Skinnar
Publisher: PUBLIC LIBRARY SCIENCE
Publication year: 2019
Journal: PLoS ONE
Journal name in source: PLOS ONE
Journal acronym: PLOS ONE
Article number: ARTN e0217291
Volume: 14
Issue: 5
Number of pages: 13
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0217291
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/45581946
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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