DOI: http://dx.doi.org/10.22516/25007440.70

Alcohol, cirrosis y predisposición genética

Mónica Marcela Gaviria, Gonzalo Correa Arango, María Cristina Navas

Resumen


La cirrosis hepática es la tercera causa de muerte alrededor del mundo que es atribuible al consumo de alcohol. Más del 80% de los consumidores crónicos de alcohol desarrollan esteatosis y entre el 20% al 40% presentan otras complicaciones como fibrosis, hepatitis alcohólica y cirrosis; sin embargo, no todos los individuos con consumo crónico de alcohol desarrollan cirrosis, en parte debido al componente genético de cada individuo. El grado de actividad de las enzimas que metabolizan el alcohol está influenciado por polimorfismos presentes en los genes que codifican para estas enzimas, y corresponde a uno de los factores determinantes para el desarrollo de una hepatopatía terminal en respuesta al consumo de alcohol. Entre las enzimas implicadas en el metabolismo del alcohol están la alcohol deshidrogenasa (ADH), el citocromo P450 2E1 (CYP2E1) y la acetaldehído deshidrogenasa (ALDH), de las cuales se ha reportado que la mayor actividad de ADH y CYP2E1 y la menor actividad de ALDH pueden conferir riesgo en algunas poblaciones por la acumulación de acetaldehído, el cual es tóxico para el organismo.

Se realizó una revisión en la literatura de los principales aspectos del metabolismo del alcohol y polimorfismos (genotipos) de enzimas que intervienen en el metabolismo del alcohol como factor de riesgo. Esto se hizo mediante la búsqueda de material bibliográfico a través de la base de datos PubMed desde 1990 hasta el 2013 utilizando las palabras claves alcohol liver disease, ADH, ALDH, CYP2E1 y polymorphism.

Palabras clave


Hepatopatía alcohólica; ADH; ALDH; CYP2E1; polimorfismo

Texto completo:

PDF

Referencias


Organization WH. Global status report on alcohol and health. Geneva: World Health Organization 2014 [citado 9 de septiembre de 2014]. Available from: http://www.who.int/iris/bitstream/10665/112736/1/9789240692763_eng.pdf?ua=1Available from: http://www.who.int/substance_abuse/publications/global_alcohol_report/en/

Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet. 2009;373(9682):2223-33.

Zakhari S. Overview: How is alcohol metabolized by the body? Alcohol Res Health. 2006;29(4):245-54.

Homann N, Stickel F, Konig IR, Jacobs A, Junghanns K, Benesova M, et al. Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers. Int J Cancer. 2006;118(8):1998-2002.

Yokoyama A, Mizukami T, Matsui T, Yokoyama T, Kimura M, Matsushita S, et al. Genetic Polymorphisms of Alcohol Dehydrogenase-1B and Aldehyde Dehydrogenase-2 and Liver Cirrhosis, Chronic Calcific Pancreatitis, Diabetes Mellitus, and Hypertension Among Japanese Alcoholic Men. Alcohol Clin Exp Res. 2013;37(8):1391-401.

Wang Y, Millonig G, Nair J, Patsenker E, Stickel F, Mueller S, et al. Ethanol-induced cytochrome P4502E1 causes carcinogenic etheno-DNA lesions in alcoholic liver disease. Hepatology. 2009;50(2):453-61.

Baraona E, Lieber CS. Effects of ethanol on lipid metabolism. J Lipid Res. 1979;20(3):289-315.

Guynn RW, Pieklik JR. Dependence on dose of the acute effects of ethanol on liver metabolism in vivo. J Clin In est. 1975;56(6):1411-9.

Lundquist F, Tygstrup N, Winkler K, Jensen KB. Glycerol metabolism in the human liver: Inhibition by ethanol. Science. 1965;150(3696):616-7.

Korsten MA, Matsuzaki S, Feinman L, Lieber CS. High blood acetaldehyde levels after ethanol administration. Difference between alcoholic and nonalcoholic subjects. N Engl J Med. 1975;292(8):386-9.

Minana JB, Gomez-Cambronero L, Lloret A, Pallardo FV, Del Olmo J, Escudero A, et al. Mitochondrial oxidative stress and CD95 ligand: A dual mechanism for hepatocyte apoptosis in chronic alcoholism. Hepatology. 2002;35(5):1205-14.

Lefevre AF, DeCarli LM, Lieber CS. Effect of ethanol on cholesterol and bile acid metabolism. J Lipid Res. 1972;13(1):48-55.

Crouse JR, Gerson CD, DeCarli LM, Lieber CS. Role of acetate in the reduction of plasma free fatty acids produced by ethanol in man. J Lipid Res. 1968;9(4):509-12.

Riveros-Rosas H, Julian-Sanchez A, Pina E. Enzymology of ethanol and acetaldehyde metabolism in mammals. Arch Med Res. 1997;28(4):453-71.

Rehm J, Shield K. Global Alcohol-Attributable deaths From Cancer, Liver Cirrhosis, and Injury in 2010 Alcohol Res Curr Rev. 2014;35(2):10.

Orman ES, Odena G, Bataller R. Alcoholic liver disease: Pathogenesis, management, and novel targets for therapy. J Gastroenterol Hepatol. 2013;28 Suppl 1:77-84.

Donato F, Tagger A, Gelatti U, Parrinello G, Boffetta P, Albertini A, et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol. 2002;155(4):323-31.

Bellentani S, Saccoccio G, Costa G, Tiribelli C, Manenti F, Sodde M, et al. Drinking habits as cofactors of risk for alcohol induced liver damage. The Dionysos Study Group. Gut. 1997;41(6):845-50.

Frezza M, di Padova C, Pozzato G, Terpin M, Baraona E, Lieber CS. High blood alcohol levels in women. The role of decreased gastric alcohol. N Engl J Med. 1990;322(2):95-9.

Hoyumpa AM, Jr., Nichols S, Henderson GI, Schenker S. Intestinal thiamin transport: Effect of chronic ethanol administration in rats. Am J Clin Nutr. 1978;31(6):938-45.

Lieber CS, DeCarli LM. An experimental model of alcohol feeding and liver injury in the baboon. J Med Primatol. 1974;3(3):153-63.

Lieber CS, Robins SJ, Li J, DeCarli LM, Mak KM, Fasulo JM, et al. Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon. Gastroenterology. 1994;106(1):152-9.

Lieber CS, DeCarli LM, Mak KM, Kim CI, Leo MA. Attenuation of alcohol-induced hepatic fibrosis by polyunsaturated lecithin. Hepatology. 1990;12(6):1390-8.

Hrubec Z, Omenn GS. Evidence of genetic predisposition to alcoholic cirrhosis and psychosis: twin concordances for alcoholism and its biological end points by zygosity among male veterans. Alcohol Clin Exp Res. 1981;5(2):207-15.

Reed T, Page WF, Viken RJ, Christian JC. Genetic Predisposition to Organ-Specific Endpoints of Alcoholism. Alcohol Clin Exp Res. 1996;20(9):1528-33.

Marrero JA, Fontana RJ, Fu S, Conjeevaram HS, Su GL, Lok AS. Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. J Hepatol. 2005;42(2):218-24.

Osier MV, Pakstis AJ, Soodyall H, Comas D, Goldman D, Odunsi A, et al. A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity. Am J Hum Genet. 2002;71(1):84-99.

Hoog JO, Ostberg LJ. Mammalian alcohol dehydrogenases: A comparative investigation at gene and protein levels. Chem Biol Interact. 2011;191(1-3):2-7.

Poupon RE, Nalpas B, Coutelle C, Fleury B, Couzigou P, Higueret D. Polymorphism of alcohol dehydrogenase, alcohol and aldehyde dehydrogenase. Hepatology. 1992;15(6):1017-22.

Carrigan MA, Uryasev O, Davis RP, Zhai L, Hurley TD, Benner SA. The natural history of class I primate alcohol dehydrogenases includes gene duplication, gene loss, and gene conversion. PLoS One. 2012;7(7):e41175.

Stewart MJ, McBride MS, Winter LA, Duester G. Promoters for the human alcohol dehydrogenase genes ADH1, ADH2, and ADH3: Interaction of CCAAT/enhancer-binding protein with elements flanking the ADH2 TATA box. Gene. 1990;90(2):271-9.

Vallee BL, Bazzone TJ. Isozymes of human liver alcohol dehydrogenase. Isozymes Curr Top Biol Med Res. 1983;8:219-44.

Duester G, Farres J, Felder MR, Holmes RS, Hoog JO, Pares X, et al. Recommended nomenclature for the vertebrate alcohol dehydrogenase gene family. Biochem Pharmacol. 1999;58(3):389-95.

Persson B, Hedlund J, Jornvall H. Medium- and short-chain dehydrogenase/reductase gene and protein families. Cell Mol Life Sci. 2008;65(24):3879-94.

Smith M, Hopkinson DA, Harris H. Alcohol dehydrogenase isozymes in adult human stomach and liver: evidence for activity of the ADH 3 locus. Ann Hum Genet. 1972;35(3):243-53.

Smith M, Hopkinson DA, Harris H. Developmental changes and polymorphism in human alcohol dehydrogenase. Ann Hum Genet. 1971;34(3):251-71.

Birley AJ, James MR, Dickson PA, Montgomery GW, Heath AC, Martin NG, et al. ADH single nucleotide polymorphism associations with alcohol metabolism in vivo. Hum Mol Genet. 2009;18(8):1533-42.

Yoshida A, Shibuya A. Polymorphisms of Alcohol and Aldehyde Dehydrogenases and Their Significance for Alcohol Liver Diseases. In: Watson R, editor. Liver Pathology and Alcohol. Drug and Alcohol Abuse Reviews. 2: Humana Press; 1991. p. 441-66.

Black WJ, Stagos D, Marchitti SA, Nebert DW, Tipton KF, Bairoch A, et al. Human aldehyde dehydrogenase genes: Alternatively spliced transcriptional. Pharmacogenet Genomics. 2009;19(11):893-902.

Hsu LC, Yoshida A, Mohandas T. Chromosomal assignment of the genes for human aldehyde dehydrogenase-1 and aldehyde dehydrogenase-2. Am J Hum Genet. 1986;38(5):641-8.

Hsu LC, Bendel RE, Yoshida A. Genomic structure of the human mitochondrial aldehyde dehydrogenase gene. Genomics. 1988;2(1):57-65.

Crabb DW, Matsumoto M, Chang D, You M. Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. Proc Nutr Soc. 2004;63(1):49-63.

Farres J, Wang X, Takahashi K, Cunningham SJ, Wang TT, Weiner H. Effects of changing glutamate 487 to lysine in rat and human liver mitochondrial aldehyde dehydrogenase. A model to study human (Oriental type) class 2 aldehyde dehydrogenase. J Biol Chem. 1994;269(19):13854-60.

Umeno M, McBride OW, Yang CS, Gelboin HV, Gonzalez FJ. Human ethanol-inducible P450IIE1: Complete gene sequence, promoter characterization, chromosome mapping, and cDNA-directed expression. Biochemistry. 1988;27(25):9006-13.

Ravindranath V, Anandatheerthavarada HK, Shankar SK. NADPH cytochrome P-450 reductase in rat, mouse and human brain. Biochem Pharmacol. 1990;39(6):1013-8.

Shen Z, Wells RL, Liu J, Elkind MM. Identification of a cytochrome P450 gene by reverse transcription--PCR using. Proc Natl Acad Sci USA. 1993;90(24):11483-7.

Lieber CS. Ethanol metabolism, cirrhosis and alcoholism. Clin Chim Acta. 1997;257(1):59-84.

Hu Y, Ingelman-Sundberg M, Lindros KO. Induction mechanisms of cytochrome P450 2E1 in liver: Interplay between ethanol treatment and starvation. Biochem Pharmacol. 1995;50(2):155-61.

Albano E, Vidali M. Immune mechanisms in alcoholic liver disease. Genes Nutr. 2010;5(2):141-7.

Bell GI, Najarian RC, Mullenbach GT, Hallewell RA. cDNA sequence coding for human kidney catalase. Nucleic Acids Res. 1986;14(13):5561-2.

Koechling UM, Amit Z. Relationship between blood catalase activity and drinking history in a human. Alcohol. 1992;27(2):181-8.

Wen JK, Osumi T, Hashimoto T, Ogata M. Molecular analysis of human acatalasemia. Identification of a splicing mutation. J Mol Biol. 1990;211(2):383-93.

Kishimoto Y, Murakami Y, Hayashi K, Takahara S, Sugimura T, Sekiya T. Detection of a common mutation of the catalase gene in Japanese acatalasemic patients. Hum Genet. 1992;88(5):487-90.

Góth L, Shemirani A, Kalmár T. A Novel Catalase Mutation (a GA Insertion) Causes the Hungarian Type of Acatalasemia. Blood Cell Mol Dis. 2000;26(2):151-4.

Farfan Labonne BE, Gutierrez M, Gomez-Quiroz LE, Konigsberg Fainstein M, Bucio L, Souza V, et al. Acetaldehyde-induced mitochondrial dysfunction sensitizes hepatocytes to oxidative damage. Cell Biol Toxicol. 2009;25(6):599-609.

Pares A, Caballería J. Patología orgánica. Adicciones. 2002;14:17.

Gao B, Bataller R. Alcoholic liver disease: Pathogenesis and new therapeutic targets. Gastroenterology. 2011; 141(5): 1572-85.

Von Wartbung JP, Papenberg J, Aebi H. An atypical human alcohol dehydrogenase. Can J Biochem. 1965:43,889.

Greenfield NJ, Pietruszko R. Two aldehyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes. Biochim Biophys Acta. 1977:483:35-45.

Harada S, Misawa S, Agarwal DP, Goedde HW. Liver alcohol dehydrogenase and aldehyde dehydrogenase in the Japanese: Isozyme. Am J Hum Genet. 1980;32(1):8-15.

Khan AJ, Husain Q, Choudhuri G, Parmar D. Association of polymorphism in alcohol dehydrogenase and interaction with other. Drug Alcohol Depen. 2010;109(1-3):190-7.

Tanaka F, Shiratori Y, Yokosuka O, Imazeki F, Tsukada Y, Omata M. High incidence of ADH2*1/ALDH2*1 genes among Japanese alcohol dependents and patients with alcoholic liver disease. Hepatology. 1996;23:234-9.

Muramatsu T, Wang ZC, Fang YR, Hu KB, Yan H, Yamada K, et al. Alcohol and aldehyde dehydrogenase genotypes and drinking behavior of Chinese living in Shanghai. Hum Genet. 1995;96(2):151-4.


Métricas de artículo

Cargando métricas ...

Metrics powered by PLOS ALM

Enlaces refback

  • No hay ningún enlace refback.


Copyright (c) 2017 Revista Colombiana de Gastroenterología

Licencia de Creative Commons
Este obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.

ISSN versión impresa 0120-9957

ISSN versión en línea 2500-7440

  Licencia de Creative Commons
Los contenidos están protegidos bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.