Screening for rare variants in the PNPLA3 gene in obese liver biopsy patients
| Autor: | An Verrijken, M. Ruppert, Evi Aerts, Peter Michielsen, Sven Francque, Fenna de Freitas, Wim Van Hul, Luc Van Gaal, Sigri Beckers, Doreen Zegers, Guy Hubens |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Nonsynonymous substitution Pathology medicine.medical_specialty Biopsy DNA Mutational Analysis Disease Bioinformatics Polymorphism Single Nucleotide 03 medical and health sciences Liver disease 0302 clinical medicine Non-alcoholic Fatty Liver Disease Nonalcoholic fatty liver disease Humans Medicine Coding region Obesity Hepatology medicine.diagnostic_test business.industry Fatty liver Gastroenterology Membrane Proteins Lipase Sequence Analysis DNA medicine.disease 030104 developmental biology Liver Liver biopsy Female 030211 gastroenterology & hepatology Human medicine business |
| Zdroj: | Clinics and research in hepatology and gastroenterology |
| ISSN: | 2210-7401 |
| DOI: | 10.1016/j.clinre.2016.05.004 |
| Popis: | Background: Previous research has clearly implicated the PNPLA3 gene in the etiology of nonalcoholic fatty liver disease as a polymorphism in the gene was found to be robustly associated to the disease. However, data on the involvement of rare PNPLA3 variants in the development of nonalcoholic fatty liver disease (NAFLD) is currently limited. Therefore, we performed an extensive mutation analysis study on a cohort of obese liver biopsy patients to determine PNPLA3 variation and its correlation with fatty liver disease. Methods: We screened the entire coding region of the PNPLA3 gene in DNA samples of 393 obese liver biopsy patients with varying degrees of fatty liver disease. Mutation analysis was performed by high-resolution melting curve analysis in combination with direct sequencing. Results: We identified several common polymorphisms as well as one rare synonymous variant (c.867G>A rs139896256), one rare intronic variant (c.979+13C>T) and 3 nonsynonymous coding variants (p.A76T, p.A104V and p.T200M) in the PNPLA3 gene. In silico analysis indicated that the p.A104V variant will probably have no functional effect, whereas for the p.A76T and p.T200M variant a possible pathogenic effect is suggested. Conclusion: Overall, we showed that novel variants in PNPLA3 are very rare in our liver biopsy cohort, thereby indicating that their impact on the etiology of NAFLD is probably limited.Nevertheless, for the three rare coding variants that were identified in patients with advance dliver disease, further functional characterization will be essential to verify their potential disease causality. (C) 2016 Elsevier Masson SAS. All rights reserved. |
| Databáze: | OpenAIRE |
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