HMOX1 genetic polymorphisms and outcomes in infectious disease: A systematic review

<h4>Introduction</h4> Heme-oxygenase 1 (HMOX1) is a critical stress response gene that catalyzes the multistep oxidation of heme. A GT(n) repeat of variable length in the promoter in has been associated with a wide range of human diseases, including infections. This paper aims to summari...

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Main Authors: Fergus W. Hamilton, Julia Somers, Ruth E. Mitchell, Peter Ghazal, Nicholas J. Timpson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098073/?tool=EBI
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author Fergus W. Hamilton
Julia Somers
Ruth E. Mitchell
Peter Ghazal
Nicholas J. Timpson
author_facet Fergus W. Hamilton
Julia Somers
Ruth E. Mitchell
Peter Ghazal
Nicholas J. Timpson
author_sort Fergus W. Hamilton
collection DOAJ
description <h4>Introduction</h4> Heme-oxygenase 1 (HMOX1) is a critical stress response gene that catalyzes the multistep oxidation of heme. A GT(n) repeat of variable length in the promoter in has been associated with a wide range of human diseases, including infections. This paper aims to summarise and systematically review associations between the length of the HMOX1 GT(n) promoter and infectious disease in humans. <h4>Methods</h4> A search using relevant terms was performed in PubMED and EMBASE through to 15/01/21 identifying all research that studied an association between the HMOX1 GT(n) repeat polymorphism and the incidence and/or outcome of any human infectious disease. Citations were screened for additional studies. Potential studies were screened for inclusion by two authors. Data was extracted on allele frequency, genotype, strength of association, mechanism of genotyping, and potential biases. A narrative review was performed across each type of infection. <h4>Results</h4> 1,533 studies were identified in the search, and one via citation screening. Sixteen studies were ultimately included, seven in malaria, three in HIV, three in sepsis, and one each in pneumonia, hepatitis C, and acute respiratory distress syndrome (ARDS). Sample sizes for nearly all studies were small (biggest study, n = 1,646). Allelic definition was different across all included studies. All studies were at some risk of bias. In malaria, three studies suggested that longer alleles were associated with reduced risk of severe malaria, particularly malaria-induced renal dysfunction, with four studies identifying a null association. In sepsis, two studies suggested an association with longer alleles and better outcomes. <h4>Conclusions</h4> Despite the importance of HMOX1 in survival from infection, and the association between repeat length and gene expression, the clinical data supporting an association between repeat length and incidence and/or outcome of infection remain inconclusive.
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spelling doaj.art-00b24f667b9246879dbe7cb5625c10232022-12-22T02:09:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01175HMOX1 genetic polymorphisms and outcomes in infectious disease: A systematic reviewFergus W. HamiltonJulia SomersRuth E. MitchellPeter GhazalNicholas J. Timpson<h4>Introduction</h4> Heme-oxygenase 1 (HMOX1) is a critical stress response gene that catalyzes the multistep oxidation of heme. A GT(n) repeat of variable length in the promoter in has been associated with a wide range of human diseases, including infections. This paper aims to summarise and systematically review associations between the length of the HMOX1 GT(n) promoter and infectious disease in humans. <h4>Methods</h4> A search using relevant terms was performed in PubMED and EMBASE through to 15/01/21 identifying all research that studied an association between the HMOX1 GT(n) repeat polymorphism and the incidence and/or outcome of any human infectious disease. Citations were screened for additional studies. Potential studies were screened for inclusion by two authors. Data was extracted on allele frequency, genotype, strength of association, mechanism of genotyping, and potential biases. A narrative review was performed across each type of infection. <h4>Results</h4> 1,533 studies were identified in the search, and one via citation screening. Sixteen studies were ultimately included, seven in malaria, three in HIV, three in sepsis, and one each in pneumonia, hepatitis C, and acute respiratory distress syndrome (ARDS). Sample sizes for nearly all studies were small (biggest study, n = 1,646). Allelic definition was different across all included studies. All studies were at some risk of bias. In malaria, three studies suggested that longer alleles were associated with reduced risk of severe malaria, particularly malaria-induced renal dysfunction, with four studies identifying a null association. In sepsis, two studies suggested an association with longer alleles and better outcomes. <h4>Conclusions</h4> Despite the importance of HMOX1 in survival from infection, and the association between repeat length and gene expression, the clinical data supporting an association between repeat length and incidence and/or outcome of infection remain inconclusive.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098073/?tool=EBI
spellingShingle Fergus W. Hamilton
Julia Somers
Ruth E. Mitchell
Peter Ghazal
Nicholas J. Timpson
HMOX1 genetic polymorphisms and outcomes in infectious disease: A systematic review
PLoS ONE
title HMOX1 genetic polymorphisms and outcomes in infectious disease: A systematic review
title_full HMOX1 genetic polymorphisms and outcomes in infectious disease: A systematic review
title_fullStr HMOX1 genetic polymorphisms and outcomes in infectious disease: A systematic review
title_full_unstemmed HMOX1 genetic polymorphisms and outcomes in infectious disease: A systematic review
title_short HMOX1 genetic polymorphisms and outcomes in infectious disease: A systematic review
title_sort hmox1 genetic polymorphisms and outcomes in infectious disease a systematic review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098073/?tool=EBI
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