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

David E. Leaf, Simon C. Body, Jochen D. Muehlschlegel, Gearoid M. McMahon, Peter Lichtner, Charles D. Collard, Stanton K. Shernan, Amanda A. Fox, Sushrut S. Waikar

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 HMOX1mRNAexpression.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, longerGT repeats in theHMOX1 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.

Original languageEnglish (US)
Pages (from-to)3291-3297
Number of pages7
JournalJournal of the American Society of Nephrology
Volume27
Issue number11
DOIs
StatePublished - 2016

Fingerprint

Heme Oxygenase-1
Thoracic Surgery
Alleles
Heme
Genotype
Confidence Intervals
Genes
Dinucleotide Repeats
Cardiopulmonary Bypass
Creatinine
Odds Ratio
Serum
Therapeutics

ASJC Scopus subject areas

  • Nephrology

Cite this

Leaf, D. E., Body, S. C., Muehlschlegel, J. D., McMahon, G. M., Lichtner, P., Collard, C. D., ... Waikar, S. S. (2016). Length polymorphisms in heme oxygenase-1 and AKI after cardiac surgery. Journal of the American Society of Nephrology, 27(11), 3291-3297. https://doi.org/10.1681/ASN.2016010038

Length polymorphisms in heme oxygenase-1 and AKI after cardiac surgery. / Leaf, David E.; Body, Simon C.; Muehlschlegel, Jochen D.; McMahon, Gearoid M.; Lichtner, Peter; Collard, Charles D.; Shernan, Stanton K.; Fox, Amanda A.; Waikar, Sushrut S.

In: Journal of the American Society of Nephrology, Vol. 27, No. 11, 2016, p. 3291-3297.

Research output: Contribution to journalArticle

Leaf, DE, Body, SC, Muehlschlegel, JD, McMahon, GM, Lichtner, P, Collard, CD, Shernan, SK, Fox, AA & Waikar, SS 2016, 'Length polymorphisms in heme oxygenase-1 and AKI after cardiac surgery', Journal of the American Society of Nephrology, vol. 27, no. 11, pp. 3291-3297. https://doi.org/10.1681/ASN.2016010038
Leaf DE, Body SC, Muehlschlegel JD, McMahon GM, Lichtner P, Collard CD et al. Length polymorphisms in heme oxygenase-1 and AKI after cardiac surgery. Journal of the American Society of Nephrology. 2016;27(11):3291-3297. https://doi.org/10.1681/ASN.2016010038
Leaf, David E. ; Body, Simon C. ; Muehlschlegel, Jochen D. ; McMahon, Gearoid M. ; Lichtner, Peter ; Collard, Charles D. ; Shernan, Stanton K. ; Fox, Amanda A. ; Waikar, Sushrut S. / Length polymorphisms in heme oxygenase-1 and AKI after cardiac surgery. In: Journal of the American Society of Nephrology. 2016 ; Vol. 27, No. 11. pp. 3291-3297.
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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 HMOX1mRNAexpression.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, longerGT repeats in theHMOX1 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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