Length Polymorphisms in Heme Oxygenase-1 and AKI after Cardiac Surgery
Open accessAbstract
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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Shorter HO-1 (GT)n alleles improve acute kidney injury and outcome after kidney transplantation in mouse models, at least partly due to increased HO-1 promoter activity.
“Shorter HO-1 (GT)n alleles have been found to improve acute kidney injury and outcome after kidney transplantation in mouse models (Leaf et al. 2016), at least partly due to the increase in HO-1 promoter activity (Gill et al. 2018).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Leaf et al. 2016
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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
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- Authors
- 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.
- Affiliations
- Division of Renal Medicine and
- Brigham and Women's Hospital (US)
- Helmholtz Munich (DE)
- Department of Anesthesiology, Baylor St. Luke’s Medical Center and the Texas Heart Institute, Houston, Texas; and
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Leaf, David E.
- McMahon, Gearoid M.
- Waikar, Sushrut S.
- ORCID
- Venue
- Journal of the American Society of Nephrology
- Published
- 2016-06-02
- Volume
- 27
- Issue
- 11
- Pages
- 3291-3297
- ISSN
- 1046-6673 (ISSN-L)
- 1533-3450
- PMC
- PMC5084897
- OpenAlex
- W2412247228
- Cited by
- 43
- References
- 35
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 9 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 3
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- University of Alabama at Birmingham
- National Heart, Lung, and Blood Institute (R01HL118266, R01HL098601)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK106448, R01DK103784, R01DK093574, U01DK085660, U01DK104308, P30DK079337)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Surgery › Cardiac and Coronary Surgery Techniques
- Keywords
- heme oxygenase-1, acute kidney injury, cardiac surgery, cardiopulmonary bypass, GT repeat polymorphism, promoter polymorphism, genetic susceptibility, heme toxicity
- MeSH terms
- Aged, Female, Cardiac Surgical Procedures, Humans, Male, Middle Aged, Polymorphism, Genetic, Postoperative Complications, Prospective Studies, Heme Oxygenase-1, Acute Kidney Injury
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