title: Prevalence of common HFE and SERPINA1 mutations in patients with hepatocellular carcinoma in a Moroccan population.
abstract: BACKGROUND
  Hereditary hemochromatosis and SERPINA1 mutation were reported to affect liver functions. Our objective was to estimate the prevalence of HFE and SERPINA1 (formerly known as alpha1-antitrypsin, AAT) mutations and assess their influence on hepatocellular carcinoma development.
  
  
  METHODS
  This study included 222 controls and 96 cases with hepatocellular carcinoma. PCR-RFLP was used to characterize S and Z alleles in SERPINA1, as well as C282Y/H63D alleles of HFE.
  
  
  RESULTS
  In healthy subjects and hepatocellular carcinoma patients as well, no homozygotes for the C282Y mutation were found. In controls, heterozygosity and homozygosity for the H63D mutation were 27 and 0.9%, respectively. Among patients, homozygosity for the H63D mutation was 3.1%, whereas heterozygosity for C282Y and H63D was 2.1 and 35.4%, respectively. Interestingly, albeit it does not reach significance (p=0.062), H63D was more prevalent in hepatocellular carcinoma patients than in controls (38.5 vs. 27.9%, respectively). The association was stronger when considering only male patients with hepatocellular carcinoma (47.1 vs. 23.6, p=0.001). Allele frequencies of S and Z in controls were 0.45% (95% CI=0.2-1.07) and 0.22% (95% CI=0.2-0.6), respectively, and 1 for S and 0% for Z in HCC. No significant difference was found between cases and controls.
  
  
  CONCLUSIONS
  We provide a novel appraisal of HFE and SERPINA1 mutations prevalence in the Moroccan population. Results are consistent with the worldwide spread of the H63D and S mutation and the north European restriction of the C282Y and Z. Our results show that H63D carriage is increased among hepatocellular carcinoma patients, suggesting that it may confer an increased susceptibility to hepatocellular carcinoma even in a heterozygous state. On the contrary, HFE C282Y and SERPINA1 mutations do not contribute to hepatocellular carcinoma development.
authors.affiliation: Laboratoire de Virologie, Institut Pasteur du Maroc, Casablanca, Morocco.
authors.forename: Sayeh
authors.initials: S
authors.lastname: Ezzikouri
authors.forename: Abdellah Essaid
authors.initials: AE
authors.lastname: El Feydi
authors.forename: Latifa
authors.initials: L
authors.lastname: El Kihal
authors.forename: Rajae
authors.initials: R
authors.lastname: Afifi
authors.forename: Mustapha
authors.initials: M
authors.lastname: Benazzouz
authors.forename: Mohammed
authors.initials: M
authors.lastname: Hassar
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Chafik
authors.forename: Pascal
authors.initials: P
authors.lastname: Pineau
authors.forename: Soumaya
authors.initials: S
authors.lastname: Benjelloun
mesh_terms: D000368:Aged; D000483:Alleles; D018912:Arabs; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009018:Morocco; D020125:Mutation, Missense; D015995:Prevalence; D012189:Retrospective Studies; D000515:alpha 1-Antitrypsin / Q000235:genetics*
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin