Role of the Common <i>PRSS1-PRSS2</i> Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses
The association between a common <i>PRSS1-PRSS2</i> 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 cont...
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MDPI AG
2020-11-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/11/1349 |
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| author | Anthony F. Herzig Emmanuelle Génin David N. Cooper Emmanuelle Masson Claude Férec Jian-Min Chen |
| author_facet | Anthony F. Herzig Emmanuelle Génin David N. Cooper Emmanuelle Masson Claude Férec Jian-Min Chen |
| author_sort | Anthony F. Herzig |
| collection | DOAJ |
| description | The association between a common <i>PRSS1-PRSS2</i> 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; <i>p</i> < 0.00001) and NACP (pooled OR 1.28, 95% CI 1.17–1.40; <i>p</i> < 0.00001). Consistent with a dosage effect of the risk allele on <i>PRSS1</i>/<i>PRSS2</i> 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. |
| first_indexed | 2024-03-10T14:51:36Z |
| format | Article |
| id | doaj.art-323f5feeab884ffe8cc5dd40445c8366 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T14:51:36Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-323f5feeab884ffe8cc5dd40445c83662023-11-20T20:53:20ZengMDPI AGGenes2073-44252020-11-011111134910.3390/genes11111349Role of the Common <i>PRSS1-PRSS2</i> Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-AnalysesAnthony F. Herzig0Emmanuelle Génin1David N. Cooper2Emmanuelle Masson3Claude Férec4Jian-Min Chen5Inserm, Univ Brest, EFS, UMR 1078, GGB, F-29200 Brest, FranceInserm, Univ Brest, EFS, UMR 1078, GGB, F-29200 Brest, FranceInstitute of Medical Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UKInserm, Univ Brest, EFS, UMR 1078, GGB, F-29200 Brest, FranceInserm, Univ Brest, EFS, UMR 1078, GGB, F-29200 Brest, FranceInserm, Univ Brest, EFS, UMR 1078, GGB, F-29200 Brest, FranceThe association between a common <i>PRSS1-PRSS2</i> 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; <i>p</i> < 0.00001) and NACP (pooled OR 1.28, 95% CI 1.17–1.40; <i>p</i> < 0.00001). Consistent with a dosage effect of the risk allele on <i>PRSS1</i>/<i>PRSS2</i> 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.https://www.mdpi.com/2073-4425/11/11/1349chronic pancreatitisgene-environment interactionmeta-analysis<i>PRSS1-PRSS2</i>re-analysisrs10273639 |
| spellingShingle | Anthony F. Herzig Emmanuelle Génin David N. Cooper Emmanuelle Masson Claude Férec Jian-Min Chen Role of the Common <i>PRSS1-PRSS2</i> Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses Genes chronic pancreatitis gene-environment interaction meta-analysis <i>PRSS1-PRSS2</i> re-analysis rs10273639 |
| title | Role of the Common <i>PRSS1-PRSS2</i> Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses |
| title_full | Role of the Common <i>PRSS1-PRSS2</i> Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses |
| title_fullStr | Role of the Common <i>PRSS1-PRSS2</i> Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses |
| title_full_unstemmed | Role of the Common <i>PRSS1-PRSS2</i> Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses |
| title_short | Role of the Common <i>PRSS1-PRSS2</i> Haplotype in Alcoholic and Non-Alcoholic Chronic Pancreatitis: Meta- and Re-Analyses |
| title_sort | role of the common i prss1 prss2 i haplotype in alcoholic and non alcoholic chronic pancreatitis meta and re analyses |
| topic | chronic pancreatitis gene-environment interaction meta-analysis <i>PRSS1-PRSS2</i> re-analysis rs10273639 |
| url | https://www.mdpi.com/2073-4425/11/11/1349 |
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