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Role of the Common PRSS1-PRSS2 Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses

The association between a common PRSS1-PRSS2 haplotype and alcoholic chronic pancreatitis (ACP), which was revealed by the first genome-wide association study of chronic pancreatitis (CP), has been consistently replicated. However, the association with non-ACP (NACP) has been controversial. Herein,...

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Autores principales: Herzig, Anthony F., Génin, Emmanuelle, Cooper, David N., Masson, Emmanuelle, Férec, Claude, Chen, Jian-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697183/
https://www.ncbi.nlm.nih.gov/pubmed/33202925
http://dx.doi.org/10.3390/genes11111349
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author Herzig, Anthony F.
Génin, Emmanuelle
Cooper, David N.
Masson, Emmanuelle
Férec, Claude
Chen, Jian-Min
author_facet Herzig, Anthony F.
Génin, Emmanuelle
Cooper, David N.
Masson, Emmanuelle
Férec, Claude
Chen, Jian-Min
author_sort Herzig, Anthony F.
collection PubMed
description The association between a common PRSS1-PRSS2 haplotype and alcoholic chronic pancreatitis (ACP), which was revealed by the first genome-wide association study of chronic pancreatitis (CP), has been consistently replicated. However, the association with non-ACP (NACP) has been controversial. Herein, we sought to clarify this basic issue by means of an allele-based meta-analysis of currently available studies. We then used studies informative for genotype distribution to explore the biological mechanisms underlying the association data and to test for gene-environment interaction between the risk haplotype and alcohol consumption by means of a re-analysis. A literature search was conducted to identify eligible studies. A meta-analysis was performed using the Review Manager software. The association between the risk genotypes and NACP or ACP was tested for the best-fitting genetic model. Gene-environment interaction was estimated by both case-only and multinomial approaches. Five and eight studies were employed for the meta-analysis of ACP and NACP findings, respectively. The risk allele was significantly associated with both ACP (pooled odds ratio (OR) 1.67, 95% confidence interval (CI) 1.56–1.78; p < 0.00001) and NACP (pooled OR 1.28, 95% CI 1.17–1.40; p < 0.00001). Consistent with a dosage effect of the risk allele on PRSS1/PRSS2 mRNA expression in human pancreatic tissue, both ACP and NACP association data were best explained by an additive genetic model. Finally, the risk haplotype was found to interact synergistically with alcohol consumption.
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spelling pubmed-76971832020-11-29 Role of the Common PRSS1-PRSS2 Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses Herzig, Anthony F. Génin, Emmanuelle Cooper, David N. Masson, Emmanuelle Férec, Claude Chen, Jian-Min Genes (Basel) Article The association between a common PRSS1-PRSS2 haplotype and alcoholic chronic pancreatitis (ACP), which was revealed by the first genome-wide association study of chronic pancreatitis (CP), has been consistently replicated. However, the association with non-ACP (NACP) has been controversial. Herein, we sought to clarify this basic issue by means of an allele-based meta-analysis of currently available studies. We then used studies informative for genotype distribution to explore the biological mechanisms underlying the association data and to test for gene-environment interaction between the risk haplotype and alcohol consumption by means of a re-analysis. A literature search was conducted to identify eligible studies. A meta-analysis was performed using the Review Manager software. The association between the risk genotypes and NACP or ACP was tested for the best-fitting genetic model. Gene-environment interaction was estimated by both case-only and multinomial approaches. Five and eight studies were employed for the meta-analysis of ACP and NACP findings, respectively. The risk allele was significantly associated with both ACP (pooled odds ratio (OR) 1.67, 95% confidence interval (CI) 1.56–1.78; p < 0.00001) and NACP (pooled OR 1.28, 95% CI 1.17–1.40; p < 0.00001). Consistent with a dosage effect of the risk allele on PRSS1/PRSS2 mRNA expression in human pancreatic tissue, both ACP and NACP association data were best explained by an additive genetic model. Finally, the risk haplotype was found to interact synergistically with alcohol consumption. MDPI 2020-11-13 /pmc/articles/PMC7697183/ /pubmed/33202925 http://dx.doi.org/10.3390/genes11111349 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Herzig, Anthony F.
Génin, Emmanuelle
Cooper, David N.
Masson, Emmanuelle
Férec, Claude
Chen, Jian-Min
Role of the Common PRSS1-PRSS2 Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses
title Role of the Common PRSS1-PRSS2 Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses
title_full Role of the Common PRSS1-PRSS2 Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses
title_fullStr Role of the Common PRSS1-PRSS2 Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses
title_full_unstemmed Role of the Common PRSS1-PRSS2 Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses
title_short Role of the Common PRSS1-PRSS2 Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses
title_sort role of the common prss1-prss2 haplotype in alcoholic and non-alcoholic chronic pancreatitis: meta- and re-analyses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697183/
https://www.ncbi.nlm.nih.gov/pubmed/33202925
http://dx.doi.org/10.3390/genes11111349
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