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

Ann Hepatol. 2011 Oct-Dec;10(4):493-501.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bariatric Surgery
  • Biomarkers / blood
  • Case-Control Studies
  • Chi-Square Distribution
  • Chile / epidemiology
  • Fatty Liver / blood
  • Fatty Liver / ethnology
  • Fatty Liver / genetics*
  • Fatty Liver / pathology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Liver / pathology
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / ethnology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / pathology
  • Logistic Models
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Obesity, Morbid / blood
  • Obesity, Morbid / ethnology
  • Obesity, Morbid / genetics*
  • Obesity, Morbid / surgery
  • Odds Ratio
  • Phenotype
  • Plasminogen Activator Inhibitor 1 / blood
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index

Substances

  • Biomarkers
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human