title: Sex-related influence of angiotensin-converting enzyme polymorphisms on fibrosis progression due to recurrent hepatitis C after liver transplantation.
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.
authors.affiliation: Department of Pathology and Medicine Experimental and Clinical, Internal Medicine, Medical Liver Transplant Unit, University of Udine, P. zale S.M. della Misericordia 1, 33100 Udine, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Fabris
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Toniutto
authors.forename: Davide
authors.initials: D
authors.lastname: Bitetto
authors.forename: Rosalba
authors.initials: R
authors.lastname: Minisini
authors.forename: Ezio
authors.initials: E
authors.lastname: Fornasiere
authors.forename: Carlo
authors.initials: C
authors.lastname: Smirne
authors.forename: Mario
authors.initials: M
authors.lastname: Pirisi
mesh_terms: D000483:Alleles; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006526:Hepatitis C / Q000473:pathology / Q000601:surgery*; D006720:Homozygote; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000473:pathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012008:Recurrence; D012737:Sex Factors; D015430:Weight Gain
chemical_list: D007703:Peptidyl-Dipeptidase A