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Centro Universitario de Ciencias de la Salud de la Universidad de Guadalajara y del OPD Hospitales Civiles de Guadalajara

2005, Number s1

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Inv Salud 2005; 7 (s1)

Genetic Basis of Alcoholic liver Damage

Bastidas RBE, Delgado RV, Muñoz VJF, González HM, Ramos MME, Carrillo PMC

Language: Spanish
References: 52
Page: 55-60
PDF size: 190.54 Kb.


ABSTRACT

Alcoholic liver disease (ALD) constitutes a complex and multifactorial pathophysiological condition where specific gene variation could explain the individual response to the toxic effects of alcohol. Genetic polymorphisms influencing the pathophysiology of ALD can positively or negatively regulate the transcriptional rate or the activity of molecules which contribute to the fibrogenic process. Polymorphisms in genes coding molecules underlying the signaling triggered by bacterial lipopolisacharide, LBP and CD14, which in turn activate Kupffer cells via the nuclear transcription factor NFkB, have been reported. Likewise, genetic polymorphisms in proinflamatory molecules, TNF-α, IL-1, R-IL-1, IL-6 and IL-8; growth factors, TGF-β and PDGF; alcohol metabolizing enzymes ADH, ALDH and CYP2E1; and in systems involved in the clearance of oxygen reactive species, like MnSOD, have been studied. Interaction between genetic variations and life-style or environmental factors, should be considered in order to elucidate the role of genetic alterations in the development of the ALD.


REFERENCES

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  8. Reeves HL, Friedman SL. Activation of hepatic stellate cells, a key issue in liver fibrosis. Front Biosci, 2002;7:d808-d826.

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  30. Achord JL. Alcohol and the liver. Sci Am Sci Med, 1995;2(2):16-25.

  31. Lieber C.S. Alcoholic liver disease: new insights in pathogenesis lead to new treatments. J Hepatol, 2000;32:113-28.

  32. Pares A, Caballería J, Bruguera M, Torres M, Rodes J. Histologic course of alcoholic hepatitis: influence of abstinense, sex and extent of hepatic damage. J Hepatol, 1986;2:33-42.

  33. Bataller R, North KE, Brenner DA. Genetic polymorphism and the progression of liver fibrosis: a critical appraisal. Hepatol, 2003;37(3):493-503.

  34. Reeves HL, Friedman SL. Activation of hepatic stellate cells, a key issue in liver fibrosis. Front Biosci, 2002;7:d808-d826.

  35. Jiménez W, Claria J, Arroyo V, Rodés J. Carbon tetrachloride induced cirrhosis in rats: a useful tool for investigating the pathogenesis of ascites in chronic liver disease. J Gastroenterol Hepatol, 1992;7:90-97. 10. Lieber CS. Alcoholic liver disease; Metabolism of alcohol. Clin Liver Dis, 1998; 2(4):1-17.

  36. Doherty DG, Norris S, Madrigal-Estebas L, McEntee G, Traynor O, Hegarty JE, O’Farrelly C. The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns. J Immunol, 1999;163:2314-2321.

  37. Ghany M, Hoofnagle JH. Estudio del paciente con enfermedad hepática. En: Harrison. Principios de Medicina Interna. Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL. McGraw Hill Interamericana, 2002; 15ª edición, sec. 2, cap. 292:1995-2000.

  38. Nanji AA, Khettry U, Sadrzady SM, Yamanaka T. Severity of liver injury in experimental alcoholic liver disease. Correlation with plasma endotoxin, prostaglandin E2, leukotriene B4, and thromboxane B2. Am J Pathol, 1993;142:367-373.

  39. Su GL. Lipopolysaccharides in liver injury: molecular mechanism of Kupffer cell activation. Am J Physiol Gastrointest Liver Physiol, 2002;283:G256-G265.

  40. Diehl A. Cytokines and the molecular mechanisms of alcoholic liver disease. Alcoholism: Clin Exp Res, 1999;23:1419-1424.

  41. McClain CJ, Barve S, Deaciuc I, Kugelmas M, Hill D. Cytokines in alcoholic liver disease. Sem Liv Dis, 1999;19:205-219.

  42. Thurman RG. Alcoholic liver injury involves activation of Kupffer cells by endotoxin. Am J Physiol, 1998;275:G605-611.

  43. Lieber CS. Microsomal ethanol-oxidizing system (MEOS): the first 30 years (1968-1998) - a review. Alcoholism: Clin Exp Res, 1999;23:991-1007.

  44. Donaldson P, Agarwal K, Craggs A, Craig W, James O, Jones D. HLA and interleukin 1 gene polymorphism in primary biliary cirrosis: association with disease progression and disease susceptibility. Gut,2001;48:397-402.

  45. Monzoni A, Masutti F, Saccoccio G, Bellentani S, Tiribelli C, Giacca M. Genetic determinants of ethanol-induced liver damage. Mol Med, 2001;7:255-262.

  46. Okamoto K, Murawaki Y, Yuasa AI, Kawasaki H. Effect of ALDH2 and CYP2E1 gene polymorphisms on drinking behavior and alcoholic liver disease in Japanese male workers. Alcohol: Clin Exp Res, 2001;25:(Suppl):19S-23S.

  47. Lee HC, Lee HS, Jung SH. Association between polymorphisms of ethanol-metabolizing enzymes and susceptibility to alcoholic cirrhosis in a Korean male population. J Korean Med Sci, 2001;16:745-750.

  48. Grove J, Daly AK, Bassendine MF, Day CP. Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis. Hepatol, 1997;26:143-146.

  49. Jarvelainen HA, Orpana A, Perola M, Savolainen VT, Karhunen PJ, Lindros KO. Promoter polymorphism of the CD14 endotoxin receptor gene as a risk factor for alcoholic liver disease. Hepatol, 2001;33:1148-1153.

  50. Stewart S, Jones D, Day CP. Alcoholic liver disease: new insights into mechanisms and preventative strategies. Trends Mol Med, 2001;7:408-413.

  51. Degoul F, Sutton A, Mansouri A. Homozygosity for alanine in the mitochondrial targeting sequence of superoxide dismutase and risk for severe alcoholic liver disease. Gastroenterol, 2001;120:1468-1474.

  52. Deuteronomio, capítulo 30, v.19. En: La Biblia al día, 1979.




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