Genetic Variants of Alcohol Metabolizing Enzymes and Alcohol-Related Liver Cirrhosis Risk
| Autor: | José A. G. Agúndez, Elena García-Martín, José M. Ladero, Jose A. Cornejo-Garcia, Pedro Ayuso |
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| Přispěvatelé: | [Ayuso,P, García-Martín,E, Agúndez,JAG] ARADyAL, Instituto de Salud Carlos III, University Institute of Molecular Pathology Biomarkers, UEx, Cáceres, Spain. [Cornejo-García,JA] ARADyAL, Instituto de Salud Carlos III Research Laboratory, IBIMA, Regional University Hospital of Málaga, UMA, Málaga, Spain. [Ladero,JM] Service of Gastroenterology (Liver Unit), Hospital Clínico San Carlos, Universidad Complutense Medical School, Madrid, Spain., The present study has been supported in part by Grants PI15/00303, PI18/00540, and RETICS ARADyAL RD16/0006/0004 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Madrid, Spain, and IB16170 and GR18145 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Union. P. A. holds a 'Atracción y retorno de talento investigador' grant by Junta de Extremadura, Spain: TA18025. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cirrhosis
alcohol-related liver disease Medicine (miscellaneous) Cirrosis hepática Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism Genetic::Genomic Structural Variation::DNA Copy Number Variations [Medical Subject Headings] Bioinformatics single nucleotide variations Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] chemistry.chemical_compound Liver disease Variaciones del número de copias de ADN 0302 clinical medicine Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation::Sequence Deletion::Gene Deletion [Medical Subject Headings] Copy-number variation 0303 health sciences Alcohol-related liver disease Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings] Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms [Medical Subject Headings] alcohol dehydrogenase ADH1B ADH1A Polimorfismo de nucleótido único Medicine Gastroenterología y hepatología Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Hemeproteins::Cytochromes::Cytochrome P-450 Enzyme System::Aryl Hydrocarbon Hydroxylases::Cytochrome P-450 CYP2E1 [Medical Subject Headings] Medicina Chemicals and Drugs::Nucleic Acids Nucleotides and Nucleosides::Nucleotides [Medical Subject Headings] Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Analysis of Variance::Multivariate Analysis [Medical Subject Headings] Diseases::Digestive System Diseases::Liver Diseases::Liver Cirrhosis [Medical Subject Headings] Article Single nucleotide variations 03 medical and health sciences CYP2E1 Gene medicine Copy number variations Ethanol metabolism Allele Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings] 030304 developmental biology business.industry cirrhosis Alcohol dehydrogenase Alcohol deshidrogenasa medicine.disease copy number variations chemistry Hepatopatías Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings] Trastornos relacionados con alcohol business 030217 neurology & neurosurgery |
| Zdroj: | E-Prints Complutense. Archivo Institucional de la UCM instname Journal of Personalized Medicine Volume 11 Issue 5 Journal of Personalized Medicine, Vol 11, Iss 409, p 409 (2021) |
| Popis: | Alcohol-related liver disease (ARLD) is a major public health issue caused by excessive alcohol consumption. ARLD encompasses a wide range of chronic liver lesions, alcohol-related liver cirrhosis being the most severe and harmful state. Variations in the genes encoding the enzymes, which play an active role in ethanol metabolism, might influence alcohol exposure and hence be considered as risk factors of developing cirrhosis. We conducted a case-control study in which 164 alcohol-related liver cirrhosis patients and 272 healthy controls were genotyped for the following functional single nucleotide variations (SNVs): ADH1B gene, rs1229984, rs1041969, rs6413413, and rs2066702 ADH1C gene, rs35385902, rs283413, rs34195308, rs1693482, and rs35719513 CYP2E1 gene, rs3813867. Furthermore, copy number variations (CNVs) for ADH1A, ADH1B, ADH1C, and CYP2E1 genes were analyzed. A significant protective association with the risk of developing alcohol-related liver cirrhosis was observed between the mutant alleles of SNVs ADH1B rs1229984 (Pcvalue = 0.037) and ADH1C rs283413 (Pc value = 0.037). We identified CNVs in all genes studied, ADH1A gene deletions being more common in alcohol-related liver cirrhosis patients than in control subjects, although the association lost statistical significance after multivariate analyses. Our findings support that susceptibility to alcohol-related liver cirrhosis is related to variations in alcohol metabolism genes. |
| Databáze: | OpenAIRE |
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