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Leaf, D.E.* ; Body, S.C.* ; Muehlschlegel, J.D.* ; McMahon, G.M.* ; Lichtner, P. ; Collard, C.D.* ; Shernan, S.K.* ; Fox, A.A.* ; Waikar, S.S.*

Length polymorphisms in heme oxygenase-1 and AKI after cardiac surgery.

J. Am. Soc. Nephrol. 27, 3291-3297 (2016)
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Heme oxygenase-1 (HO-1) catalyzes the degradation of heme, which may be involved in the pathogenesis of AKI. Length polymorphisms in the number of GT dinucleotide repeats in the HO-1 gene (HMOX1) promoter inversely associate with HMOX1 mRNA expression. We analyzed the association between allelic frequencies of GT repeats in the HMOX1 gene promoter and postoperative AKI in 2377 white patients who underwent cardiac surgery with cardiopulmonary bypass. We categorized patients as having the short allele (S; <27 GT repeats) or long allele (L; ≥27 GT repeats), and defined AKI as an increase in serum creatinine ≥0.3 mg/dl within 48 hours or ≥50% within 5 days, or the need for RRT. Compared with patients with the SS genotype, patients with the LL genotype had 1.58-fold (95% confidence interval, 1.06 to 2.34; P=0.02) higher odds of AKI. After adjusting for baseline and operative characteristics, the odds ratio for AKI per L allele was 1.26 (95% confidence interval, 1.05 to 1.50; P=0.01). In conclusion, longer GT repeats in the HMOX1 gene promoter associate with increased risk of AKI after cardiac surgery, consistent with heme toxicity as a pathogenic feature of cardiac surgery-associated AKI, and with HO-1 as a potential therapeutic target.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Acute Renal Failure ; Heme Oxygenase ; Human Genetics; Acute Kidney Injury; Acute-renal-failure; Coronary-artery-disease; Microsatellite Polymorphism; Ischemia-reperfusion; Rheumatoid-arthritis; Promoter; Iron; Mortality; Heme-oxygenase-1
Language english
Publication Year 2016
HGF-reported in Year 2016
ISSN (print) / ISBN 1046-6673
e-ISSN 1533-3450
Journal Journal of the American Society of Nephrology
Quellenangaben Volume: 27, Issue: 11, Pages: 3291-3297 Article Number: , Supplement: ,
Publisher American Society of Nephrology
Publishing Place Washington
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500700-001
DOI 10.1681/ASN.2016010038
WOS ID WOS:000386538300011
PubMed ID 27257045
Erfassungsdatum 2016-06-06
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