Ayuso, PedroGarcía-Martín, ElenaCornejo-García, José A.Agúndez, José A G.Ladero, José María2022-08-292022-08-292021-05-13Ayuso P, García-Martín E, Cornejo-García JA, Agúndez JAG, Ladero JM. Genetic Variants of Alcohol Metabolizing Enzymes and Alcohol-Related Liver Cirrhosis Risk. J Pers Med. 2021 May 13;11(5):409http://hdl.handle.net/10668/3961Alcohol-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 (Pc value = 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Alcohol-related liver diseaseCirrhosisSingle nucleotide variationsCopy number variationsAlcohol dehydrogenaseMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Hemeproteins::Cytochromes::Cytochrome P-450 Enzyme System::Aryl Hydrocarbon Hydroxylases::Cytochrome P-450 CYP2E1Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Genomic Structural Variation::DNA Copy Number VariationsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control StudiesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::AllelesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation::Sequence Deletion::Gene DeletionMedical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol DrinkingMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver NeoplasmsMedical Subject Headings::Diseases::Digestive System Diseases::Liver Diseases::Liver CirrhosisMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Analysis of Variance::Multivariate AnalysisMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleotidesresearch article34068303open accessTrastornos relacionados con alcoholHepatopatíasCirrosis hepáticaPolimorfismo de nucleótido únicoVariaciones del número de copias de ADNAlcohol deshidrogenasa10.3390/jpm110504092075-4426PMC8153263