Sex-related influence of angiotensin-converting enzyme polymorphisms on fibrosis progression due to recurrent hepatitis C after liver transplantation

J Gastroenterol. 2007 Jul;42(7):543-9. doi: 10.1007/s00535-007-2040-1. Epub 2007 Jul 25.

Abstract

Background: Experimental evidence and clinical studies suggest that the renin-angiotensin system and its inhibitors may play a role in regulating the mechanisms of liver fibrosis development. The present study aimed to verify whether carriage of specific angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) allelic variants, modulating angiotensin II generation, could affect the outcome of recurrent hepatitis C after liver transplantation, via several metabolic pathways.

Methods: Forty-five (29 men) recipients, with a median histological follow-up of 60 months after orthotopic liver transplantation (OLT), were studied. ACE gene I/D polymorphism was assessed by means of a polymerase chain reaction procedure. Fibrosis progression was evaluated annually during the follow-up.

Results: Weight gain 1 year post-OLT (defined as an increase in body mass index, BMI, of >0.5 kg/m(2)) was significantly more common among D/ carriers (22/22 vs. 16/23, P < 0.005); patients who 1 year after OLT had an increase in their BMI value of >0.5 kg/m(2) more frequently had a triglycerides/cholesterol ratio of <or= 0.7 (16/22 vs. 8/23, chi-squared test P < 0.02). This association was stronger in men. Female D/D homozygotes had the highest probability of showing significant liver fibrosis (7/10) in comparison with men (11/29) and I/ women (1/6) (P < 0.01).

Conclusions: In patients with recurrent hepatitis C, carriers of the D allele appeared to gain more weight after liver transplantation, and in male liver recipients, the D allele was associated with a peculiar lipid profile that was associated with a slower rate of allograft fibrosis progression. Among female recipients, carriage of the D allele may favor more severe allograft fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Deletion
  • Genetic Predisposition to Disease
  • Genotype
  • Hepatitis C / pathology
  • Hepatitis C / surgery*
  • Homozygote
  • Humans
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / virology
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / pathology
  • Male
  • Peptidyl-Dipeptidase A / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Recurrence
  • Sex Factors
  • Weight Gain

Substances

  • Peptidyl-Dipeptidase A