medigraphic.com
Órgano Oficial de la Asociación Mexicana de Hepatología

2011, Number 4

<< Back Next >>

Ann Hepatol 2011; 10 (4)

Plasminogen activator inhibitor type 1 serum levels and 4G/5G gene polymorphism in morbidly obese Hispanic patients with non-alcoholic fatty liver disease

Espino A, Villagrán A, Vollrath V, Hanckes P, Salas R, Farah A, Solís N, Pizarro M, Escalona A, Boza C, Pérez G, Carrasco G, Padilla O, Miquel JF, Nervi F, Chavez-Tapia NC, Arab JP, Álvarez-Lobos M, Arrese M, Riquelme A

Language: English
References: 43
Page: 493-501
PDF size: 74.62 Kb.


ABSTRACT

Background. The plasminogen activator inhibitor type-1 (PAI-1) has been implicated in the regulation of fibrinolysis and extracellular matrix components. The single base pair guanine insertion/deletion polymorphism (4G/5G) within the promoter region of the PAI-1 gene influences PAI-1 synthesis and may modulate hepatic fibrogenesis. Aim. To evaluate the influence of PAI-1 serum levels and 4G/5G polymorphism on the risk of liver fibrosis associated to non-alcoholic fatty liver disease (NAFLD) in morbidly obese patients. Material and methods. Case-control study of 50 obese patients undergoing bariatric surgery and 71 non-obese subjects matched by age and sex. Anthropometric and biochemical measurements were performed, including PAI-1 serum levels. Genomic DNA was obtained to assess the presence of 4G/5G polymorphism. Results. BMI, insulinemia, triglycerides, HOMA-IR, hypertension and diabetes were significantly higher in obese patients compared to control subjects. PAI-1 serum levels observed in obese patients were significantly lower (10.63 ± 4.82) compared to controls (14.26 ± 11.4; p ‹ 0.05). No differences were observed in the PAI-1 4G/5G promoter genotypes frequencies (p = 0.12). No differences were observed in PAI-1 plasma levels among obese patients with liver fibrosis (10.64 ± 4.35) compared to patients without liver fibrosis (10.61 ± 5.2; p = 0.985). PAI-1 4G/5G promoter genotypes frequencies were similar in patients with or without liver fibrosis associated to NASH (p = 0.6). Conclusions. Morbidly obese patients had significantly lower PAI-1 serum levels with similar PAI-1 4G/5G genotypes frequencies compared to non-obese subjects. The frequency of 4G/5G genotypes in Chilean Hispanic healthy subjects was similar to that described in other populations. No association was found between PAI-1 serum levels or 4G/5G genotype with liver fibrosis in obese patients.


REFERENCES

  1. Pi-Sunyer X. The medical risks of obesity. Postgrad Med 2009; 121(6): 21-33.

  2. Mendez-Sanchez N, Arrese M, Zamora-Valdes D, Uribe M. Current concepts in the pathogenesis of nonalcoholic fatty liver disease. Liver Int 2007; 27(4): 423-33.

  3. Targher G, Chonchol M, Miele L, Zoppini G, Pichiri I, Muggeo M. Nonalcoholic fatty liver disease as a contributor to hypercoagulation and thrombophilia in the metabolic syndrome. Semin Thromb Hemost 2009; 35(3): 277-87.

  4. Meshkani R, Adeli K. Hepatic insulin resistance, metabolic syndrome and cardiovascular disease. Clin Biochem 2009; 42(13-14): 1331-46.

  5. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010; 363(14): 1341-50.

  6. Kohler HP, Grant PJ. Plasminogen-activator inhibitor type 1 and coronary artery disease. N Engl J Med 2000; 342(24): 1792-801.

  7. Kargili A, Cipil H, Karakurt F, Kasapoglu B, Koca C, Aydin M, Uysal S, et al. Hemostatic alterations in fatty liver disease. Blood Coagul Fibrinolysis 2010; 21(4): 325-7.

  8. Sookoian S, Castano GO, Burgueno AL, Rosselli MS, Gianotti TF, Mallardi P, Martino JS, et al. Circulating levels and hepatic expression of molecular mediators of atherosclerosis in nonalcoholic fatty liver disease. Atherosclerosis 2009.

  9. De Taeye B, Smith LH, Vaughan DE. Plasminogen activator inhibitor- 1: a common denominator in obesity, diabetes and cardiovascular disease. Curr Opin Pharmacol 2005; 5(2): 149-54.

  10. Diamond MP, El-Hammady E, Wang R, Kruger M, Saed G. Regulation of expression of tissue plasminogen activator and plasminogen activator inhibitor-1 by dichloroacetic acid in human fibroblasts from normal peritoneum and adhesions. Am J Obstet Gynecol 2004; 190(4): 926-34.

  11. Bergheim I, Guo L, Davis MA, Duveau I, Arteel GE. Critical role of plasminogen activator inhibitor-1 in cholestatic liver injury and fibrosis. J Pharmacol Exp Ther 2006; 316(2): 592-600.

  12. von Montfort C, Beier JI, Kaiser JP, Guo L, Joshi-Barve S, Pritchard MT, States JC, et al. PAI-1 plays a protective role in CCl4-induced hepatic fibrosis in mice: role of hepatocyte division. Am J Physiol Gastrointest Liver Physiol 2010; 298(5): G657-G666.

  13. Heaton JH, Dlakic WM, Gelehrter TD. Posttranscriptional regulation of PAI-1 gene expression. Thromb Haemost 2003; 89(6): 959-66.

  14. Thuy S, Ladurner R, Volynets V, Wagner S, Strahl S, Konigsrainer A, Maier KP, et al. Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake. J Nutr 2008; 138(8): 1452-5.

  15. Alisi A, Manco M, Devito R, Piemonte F, Nobili V. Endotoxin and plasminogen activator inhibitor-1 serum levels associated with nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr 2010; 50(6): 645-9.

  16. Hermans PW, Hazelzet JA. Plasminogen activator inhibitor type 1 gene polymorphism and sepsis. Clin Infect Dis 2005; 41(Suppl. 7): S453-S458.

  17. Wingeyer SD, Belli SH, Graffigna MN, Levalle O, de Larranaga GF. Relationship between 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene and obesity in Argentinian Hispanic adults. Blood Coagul Fibrinolysis 2010; 21(2): 196-8.

  18. Armendariz-Borunda J, Rincon AR, Munoz-Valle JF, Bueno-Topete M, Oregon-Romero E, Islas-Carbajal MC, Medina-Preciado D, et al. Fibrogenic polymorphisms (TGF-beta, PAI-1, AT) in Mexican patients with established liver fibrosis. Potential correlation with pirfenidone treatment. J Investig Med 2008; 56(7): 944-53.

  19. Ruhl CE, Everhart JE. Epidemiology of nonalcoholic fatty liver. Clin Liver Dis 2004; 8(3): 501-19, vii.

  20. Miquel JF, Covarrubias C, Villaroel L, Mingrone G, Greco AV, Puglielli L, Carvallo P, et al. Genetic epidemiology of cholesterol cholelithiasis among Chilean Hispanics, Amerindians, and Maoris. Gastroenterology 1998; 115(4): 937-46.

  21. Riquelme A, Arrese M, Soza A, Morales A, Baudrand R, Perez- Ayuso RM, Gonzalez R, et al. Non-alcoholic fatty liver disease and its association with obesity, insulin resistance and increased serum levels of C-reactive protein in Hispanics. Liver Int 2009; 29(1): 82-8.

  22. Charatcharoenwitthaya P, Lindor KD. Role of radiologic modalities in the management of non-alcoholic steatohepatitis. Clin Liver Dis 2007; 11(1): 37-54, viii.

  23. Mishra P, Younossi ZM. Abdominal ultrasound for diagnosis of nonalcoholic fatty liver disease (NAFLD). Am J Gastroenterol 2007; 102(12): 2716-7.

  24. Matson GA, Sutton HE, Etcheverry RB, Swanson J, Robinson A. Distribution of hereditary blood groups among Indians in South America. IV. In Chile. Am J Phys Anthropol 1970; 27: 157-94.

  25. Chakaraborty R. Gene admixture in human populations, models and predictions. Yearbook Phys Anthropol 1986; 29: 1-43.

  26. Wigginton JE, Cutler DJ, Abecasis GR. A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 2005; 76(5): 887-93.

  27. Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, Monauni T, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 2000; 23(1): 57-63.

  28. Acosta AM, Escalona M, Maiz A, Pollak F, Leighton F. Determination of the insulin resistance index by the Homeostasis Model Assessment in a population of Metropolitan Region in Chile. Rev Med Chil 2002; 130(11): 1227-31.

  29. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/ National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112(17): 2735-52.

  30. Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003; 124(1): 71-9.

  31. American Diabetes Association. Standards of medical care in diabetes 2007. Diabetes Care 2007; 30(Suppl. 1): S4-S41.

  32. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001; 285(19): 2486-97.

  33. Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement. Am J Clin Nutr 1992; 55(2 Suppl.): 615S-619S.

  34. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41(6): 1313-21.

  35. Rossaak JI, Van Rij AM, Jones GT, Harris EL. Association of the 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor-1 with abdominal aortic aneurysms. J Vasc Surg 2000; 31(5): 1026-32.

  36. Chen CH, Eng HL, Chang CJ, Tsai TT, Lai ML, Chen HY, Liu CJ, et al. 4G/5G promoter polymorphism of plasminogen activator inhibitor-1, lipid profiles, and ischemic stroke. J Lab Clin Med 2003; 142(2): 100-5.

  37. Ruiz-Quezada S, Vazquez-Del Mercado M, Parra-Rojas I, Rangel-Villalobos H, Best-Aguilera C, Sanchez-Orozco LV, Munoz-Valle JF. Genotype and allele frequency of PAI-1 promoter polymorphism in healthy subjects from the west of Mexico. Association with biochemical and hematological parameters. Ann Genet 2004; 47(2): 155-62.

  38. Henry M, Chomiki N, Scarabin PY, Alessi MC, Peiretti F, Arveiler D, Ferrieres J, et al. Five frequent polymorphisms of the PAI-1 gene: lack of association between genotypes, PAI activity, and triglyceride levels in a healthy population. Arterioscler Thromb Vasc Biol 1997; 17(5): 851-8.

  39. Naderi J, Bernreuther C, Grabinski N, Putman CT, Henkel B, Bell G, Glatzel M, et al. Plasminogen activator inhibitor type 1 up-regulation is associated with skeletal muscle atrophy and associated fibrosis. Am J Pathol 2009; 175(2): 763-71.

  40. Siddiquee K, Hampton J, Khan S, Zadory D, Gleaves L, Vaughan DE, Smith LH. Apelin protects against angiotensin II-induced cardiovascular fibrosis and decreases plasminogen activator inhibitor type-1 production. J Hypertens 2011; 29(4): 724-31.

  41. Kinik ST, Atac FB, Verdi H, Cetintas S, Sahin FI, Ozbek N. The effect of plasminogen activator inhibitor-1 gene 4G/ 5G polymorphism on glucose and lipid metabolisms in Tur kish obese children. Clin Endocrinol 2005; 62(5): 607-10.

  42. Kinik ST, Ozbek N, Yuce M, Yazici AC, Verdi H, Atac FB. PAI-1 gene 4G/5G polymorphism, cytokine levels and their relations with metabolic parameters in obese children. Thromb Haemost 2008; 99(2): 352-6.

  43. Yener S, Akarsu M, Demir T, Akinci B, Sagol O, Bayraktar F, Ozcan MA, et al. Plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor levels in nonalcoholic steatohepatitis. J Endocrinol Invest 2007; 30(10): 810-9.




2020     |     www.medigraphic.com