Association of Functional Heme Oxygenase-1 Gene Promoter Polymorphism with Renal Transplantation Outcomes

Courtney, Aisling E.; McNamee, P; Middleton, Derek; Heggarty, Shirley; Patterson, Christopher; Maxwell, Alexander P.

doi:10.1111/j.1600-6143.2006.01726.x

Cited by 45 publications

(40 citation statements)

References 20 publications

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“…In support of this finding, no evidence of a protective effect for short alleles, i.e., low (GT) 2 repeat, for graft or recipient survival in clinical renal transplant was seen (Courtney et al, 2007). In a study of 3104 patients with vascular disease, restenosis after percutaneous coronary intervention was associated with angiotensin II-type l receptor 116 A/C polymorphism but was not associated with polymorphism of HO-1 (Wijpkema et al, 2006).…”

Section: Apoptosis Necrosissupporting

confidence: 52%

Pharmacological and Clinical Aspects of Heme Oxygenase

Abraham

Kappas²

2008

Pharmacol Rev

1,010

988

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Section: Apoptosis Necrosissupporting

confidence: 52%

Pharmacological and Clinical Aspects of Heme Oxygenase

Abraham

Kappas²

2008

Pharmacol Rev

1,010

988

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“…Association between HMOX1 polymorphisms and several disease conditions have been proposed, including chronic obstructive pulmonary disease, vascular restenosis, and rheumatoid arthritis (56)(57)(58)(59)(60). A recent study has described an association between HMOX1 promoter length polymorphisms and renal function after renal transplantation (61), though similar studies report no associations in the outcome of cardiac or renal transplantation (62,63). Though additional studies are required before a consensus can be reached, these observations suggest that a genetically dependent down-regulation of HO-1 expression may arise in subpopulations, possibly linked to increased susceptibility to oxidative stress and associated disease conditions.…”

Section: Heme Oxygenase-1: Gene Regulationmentioning

confidence: 87%

Heme Oxygenase-1/Carbon Monoxide

Ryter

Choi

2009

Am J Respir Cell Mol Biol

260

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Heme oxygenase-1 (HO-1), a ubiquitous inducible stress-response protein, serves a major metabolic function in heme turnover. HO activity cleaves heme to form biliverdin-IXa, carbon monoxide (CO), and iron. Genetic experiments have revealed a central role for HO-1 in tissue homeostasis, protection against oxidative stress, and in the pathogenesis of disease. Four decades of research have witnessed not only progress in elucidating the molecular mechanisms underlying the regulation and function of this illustrious enzyme, but also have opened remarkable translational applications for HO-1 and its reaction products. CO, once regarded as a metabolic waste, can act as an endogenous mediator of cellular signaling and vascular function. Exogenous application of CO by inhalation or pharmacologic delivery can confer cytoprotection in preclinical models of lung/vascular injury and disease, based on anti-apoptotic, antiinflammatory, and anti-proliferative properties. The bile pigments, biliverdin and bilirubin, end products of heme degradation, have also shown potential as therapeutics in vascular disease based on anti-inflammatory and anti-proliferative activities. Further translational and clinical trials research will unveil whether the HO-1 system or any of its reaction products can be successfully applied as molecular medicine in human disease.

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“…Unfortunately, this SNP was not tested in the two previous studies in kidney transplant recipients. Moreover, a third large genetic association study between the (GT) n polymorphism and outcome after kidney transplantation did not provide evidence for a protective effect of class S alleles on kidney graft survival (36). The LD between the short (GT) n variant and the T-allele at -413 in the current study, in combination with the known dominant effect of the A(-413)T SNP in relation to the (GT) n polymorphism (16), could possibly explain the inconsistent results of studies in kidney transplant recipients focusing on the (GT) n polymorphism only.…”

Section: Discussionmentioning

confidence: 98%

Heme Oxygenase-1 Genotype of the Donor Is Associated With Graft Survival After Liver Transplantation

Buis

Steege

Visser

et al. 2008

American Journal of Transplantation

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Heme oxygenase-1 (HO-1) has been suggested as a cytoprotective gene during liver transplantation. Inducibility of HO-1 is modulated by a (GT) n polymorphism and a single nucleotide polymorphism (SNP) A(-413)T in the promoter. Both a short (GT) n allele and the A-allele have been associated with increased HO-1 promoter activity. In 308 liver transplantations, we assessed donor HO-1 genotype and correlated this with outcome variables. For (GT) n genotype, livers were divided into two classes: short alleles (<25 repeats; class S) and long alleles (≥25 repeats; class L). In a subset, hepatic messenger ribonucleic acid (mRNA) expression was correlated with genotypes. Graft survival at 1 year was significantly better for A-allele genotype compared to TT-genotype (84% vs. 63%, p = 0.004). Graft loss due to primary dysfunction (PDF) occurred more frequently in TT-genotype compared to A-receivers (p = 0.03). Recipients of a liver with TT-genotype had significantly higher serum transaminases after transplantation and hepatic HO-1 mRNA levels were significantly lower compared to the A-allele livers (p = 0.03). No differences were found for any outcome variable between class S and LL-variant of the (GT) n polymorphism. Haplotype analysis confirmed dominance of the A(-413)T SNP over the (GT) n polymorphism. In conclusion, HO-1 genotype is associated with outcome after liver transplantation. These findings suggest that HO-1 mediates graft survival after liver transplantation.

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Association of Functional Heme Oxygenase-1 Gene Promoter Polymorphism with Renal Transplantation Outcomes

Cited by 45 publications

References 20 publications

Pharmacological and Clinical Aspects of Heme Oxygenase

Pharmacological and Clinical Aspects of Heme Oxygenase

Heme Oxygenase-1/Carbon Monoxide

Heme Oxygenase-1 Genotype of the Donor Is Associated With Graft Survival After Liver Transplantation

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