title: Length Polymorphisms in Heme Oxygenase-1 and AKI after Cardiac Surgery.
abstract: 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.
authors.affiliation: Division of Renal Medicine and DELEAF@partners.org.
authors.forename: David E
authors.initials: DE
authors.lastname: Leaf
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Body
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Jochen D
authors.initials: JD
authors.lastname: Muehlschlegel
authors.affiliation: Division of Renal Medicine and.
authors.forename: Gearoid M
authors.initials: GM
authors.lastname: McMahon
authors.affiliation: Genome Analysis Center, Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.affiliation: Department of Anesthesiology, Baylor St. Luke's Medical Center and the Texas Heart Institute, Houston, Texas; and.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Collard
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Stanton K
authors.initials: SK
authors.lastname: Shernan
authors.affiliation: Department of Anesthesiology and Pain Management, and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Fox
authors.affiliation: Division of Renal Medicine and.
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
mesh_terms: D058186:Acute Kidney Injury / Q000201:enzymology* / Q000235:genetics*; D000368:Aged; D006348:Cardiac Surgical Procedures; D005260:Female; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000201:enzymology* / Q000235:genetics*; D011446:Prospective Studies
chemical_list: D051547:Heme Oxygenase-1
keywords: acute renal failure; heme oxygenase; human genetics