Genetic Polymorphisms Implicated in Nonalcoholic Liver Disease or Selected Other Disorders Have No Influence on Drug‐Induced Liver Injury
With the application of genetic testing to contemporary medical diagnostics and practice, it has become apparent that the phenotypes of many disorders are modulated by host genetic factors. The aim of the current study was to determine whether selected single nucleotide polymorphisms (SNPs) unrelate...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2019-08-01
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| Series: | Hepatology Communications |
| Online Access: | https://doi.org/10.1002/hep4.1382 |
| _version_ | 1797706460241592320 |
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| author | Herbert L. Bonkovsky Tyler Severson Paola Nicoletti Huiman Barnhart Jose Serrano Naga Chalasani Robert J. Fontana Paul B. Watkins Victor Navarro Andrew Stolz Ann K. Daly Guruparasad P. Aithal Joseph Odin the US DILIN Investigators |
| author_facet | Herbert L. Bonkovsky Tyler Severson Paola Nicoletti Huiman Barnhart Jose Serrano Naga Chalasani Robert J. Fontana Paul B. Watkins Victor Navarro Andrew Stolz Ann K. Daly Guruparasad P. Aithal Joseph Odin the US DILIN Investigators |
| author_sort | Herbert L. Bonkovsky |
| collection | DOAJ |
| description | With the application of genetic testing to contemporary medical diagnostics and practice, it has become apparent that the phenotypes of many disorders are modulated by host genetic factors. The aim of the current study was to determine whether selected single nucleotide polymorphisms (SNPs) unrelated to the human leukocyte antigen region or other immune pathways, including those associated with nonalcoholic fatty liver disease (NAFLD), may influence development, severity, or outcomes of drug‐induced liver injury (DILI). Thirteen variants previously associated with NAFLD and/or selected other liver diseases were tested in 832 Caucasian DILI cases and 10,397 Caucasian population controls. DILI cases were attributed to multiple agents (177 individual drugs), with 56 cases due to herbal/dietary supplement products. Allele frequencies were imputed from recent genome‐wide association studies and compared to those for European control samples from the Gnomad database. Significance was tested by linear regression or logistic regression, depending on the nature of the trait. Any variant that passed the Bonferroni threshold of P < 0.0004 (0.0513) was considered a significant association. None of the variants proved to be significantly associated with DILI as phenotype nor with any of the selected severity traits. Among the variants studied, rs1421085, found in the fat mass and obesity associated (FTO) gene, showed a marginal protective effect (odds ratio, 0.8; 95% confidence interval, 0.77‐0.95; P = 0.005). None of the genetic polymorphisms tested were significantly associated with the risk of development, severity, or outcome of DILI. Conclusion: SNPs implicated in common liver diseases, such as NAFLD, do not play a substantial role in DILI pathogenesis across agents. It remains possible that these variants could be involved with DILI due to single agents, but this will require the evaluation of larger numbers of bona fide cases. |
| first_indexed | 2024-03-12T05:51:34Z |
| format | Article |
| id | doaj.art-778afcdb84f24174ade8e85fa6dda32c |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-03-12T05:51:34Z |
| publishDate | 2019-08-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-778afcdb84f24174ade8e85fa6dda32c2023-09-03T05:04:10ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2019-08-01381032103510.1002/hep4.1382Genetic Polymorphisms Implicated in Nonalcoholic Liver Disease or Selected Other Disorders Have No Influence on Drug‐Induced Liver InjuryHerbert L. Bonkovsky0Tyler Severson1Paola Nicoletti2Huiman Barnhart3Jose Serrano4Naga Chalasani5Robert J. Fontana6Paul B. Watkins7Victor Navarro8Andrew Stolz9Ann K. Daly10Guruparasad P. Aithal11Joseph Odin12the US DILIN InvestigatorsDepartment of Medicine, Gastroenterology and Hepatology Section Wake Forest University School of Medicine Winston‐Salem NCDepartment of Medicine, Gastroenterology and Hepatology Section Wake Forest University School of Medicine Winston‐Salem NCIcahn School of Medicine at Mount Sinai Medical Center New York NYDuke Clinical Research Institute Durham NCNational Institute of Diabetes and Digestive and Kidney Diseases Bethesda MDDivision of Gastroenterology Indiana University School of Medicine Indianapolis INDivision of Gastroenterology University of Michigan School of Medicine Ann Arbor MIDepartments of Pharmacology and Medicine University of North Carolina School of Medicine Chapel Hill NCDepartment of Medicine Einstein Medical Center Philadelphia PADivision of Gastroenterology and Hepatology University of Southern California School of Medicine Los Angeles CANewcastle University Newcastle‐upon‐Tyne United KingdomNational Institute for Health Research, Nottingham Biomedical Research Centre Nottingham University Hospitals National Health Service Trust and the University of Nottingham Nottingham United KingdomIcahn School of Medicine at Mount Sinai Medical Center New York NYWith the application of genetic testing to contemporary medical diagnostics and practice, it has become apparent that the phenotypes of many disorders are modulated by host genetic factors. The aim of the current study was to determine whether selected single nucleotide polymorphisms (SNPs) unrelated to the human leukocyte antigen region or other immune pathways, including those associated with nonalcoholic fatty liver disease (NAFLD), may influence development, severity, or outcomes of drug‐induced liver injury (DILI). Thirteen variants previously associated with NAFLD and/or selected other liver diseases were tested in 832 Caucasian DILI cases and 10,397 Caucasian population controls. DILI cases were attributed to multiple agents (177 individual drugs), with 56 cases due to herbal/dietary supplement products. Allele frequencies were imputed from recent genome‐wide association studies and compared to those for European control samples from the Gnomad database. Significance was tested by linear regression or logistic regression, depending on the nature of the trait. Any variant that passed the Bonferroni threshold of P < 0.0004 (0.0513) was considered a significant association. None of the variants proved to be significantly associated with DILI as phenotype nor with any of the selected severity traits. Among the variants studied, rs1421085, found in the fat mass and obesity associated (FTO) gene, showed a marginal protective effect (odds ratio, 0.8; 95% confidence interval, 0.77‐0.95; P = 0.005). None of the genetic polymorphisms tested were significantly associated with the risk of development, severity, or outcome of DILI. Conclusion: SNPs implicated in common liver diseases, such as NAFLD, do not play a substantial role in DILI pathogenesis across agents. It remains possible that these variants could be involved with DILI due to single agents, but this will require the evaluation of larger numbers of bona fide cases.https://doi.org/10.1002/hep4.1382 |
| spellingShingle | Herbert L. Bonkovsky Tyler Severson Paola Nicoletti Huiman Barnhart Jose Serrano Naga Chalasani Robert J. Fontana Paul B. Watkins Victor Navarro Andrew Stolz Ann K. Daly Guruparasad P. Aithal Joseph Odin the US DILIN Investigators Genetic Polymorphisms Implicated in Nonalcoholic Liver Disease or Selected Other Disorders Have No Influence on Drug‐Induced Liver Injury Hepatology Communications |
| title | Genetic Polymorphisms Implicated in Nonalcoholic Liver Disease or Selected Other Disorders Have No Influence on Drug‐Induced Liver Injury |
| title_full | Genetic Polymorphisms Implicated in Nonalcoholic Liver Disease or Selected Other Disorders Have No Influence on Drug‐Induced Liver Injury |
| title_fullStr | Genetic Polymorphisms Implicated in Nonalcoholic Liver Disease or Selected Other Disorders Have No Influence on Drug‐Induced Liver Injury |
| title_full_unstemmed | Genetic Polymorphisms Implicated in Nonalcoholic Liver Disease or Selected Other Disorders Have No Influence on Drug‐Induced Liver Injury |
| title_short | Genetic Polymorphisms Implicated in Nonalcoholic Liver Disease or Selected Other Disorders Have No Influence on Drug‐Induced Liver Injury |
| title_sort | genetic polymorphisms implicated in nonalcoholic liver disease or selected other disorders have no influence on drug induced liver injury |
| url | https://doi.org/10.1002/hep4.1382 |
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