title: Molecular analysis of A1AT (S and Z) and HFE (C282Y and H63D) gene mutations in Egyptian cases with HCV liver cirrhosis.
abstract: BACKGROUND
  Alpha-1-antitrypsin (A1AT) S and Z deficiency alleles and hemochromatosis (HFE) mutant C282Y, H63D alleles were reported to potentially affect the liver even if present in a heterozygous state.
  
  
  OBJECTIVE
  This is a cross-sectional, randomized, case controlled study for evaluation of the frequency of these alleles in Egyptian patients with HCV liver cirrhosis and of their association with the disease.
  
  
  METHODS
  This study included 48 cases with viral C cirrhosis recruited from the Hepatology Unit, Mansoura University Hospital, Egypt, and 70 unrelated healthy controls.
  
  
  METHODS
  PCR amplification of relevant gene segment followed by restriction enzyme digestion Taq1 for detection of A1AT gene S and Z alleles, digestion with Rsa I and Bcl I for HFE gene C282Y and H63D alleles. These alleles were then characterized through analysis of resulting restriction fragment length polymorphism (RFLP).
  
  
  RESULTS
  Both heterozygous (MS) and homozygous (SS) genotypes were significantly more frequent in cases than in controls ( P<0.05, RR= 2.23 and 2.17 respectively). Gene frequency of S allele was higher in cases than controls (P<0.05, RR=2.17). Homozygosity (ZZ) genotype, present only in cases (6.3% vs 0.0% in controls,) did not reach statistical significance. HFE gene heterozygosity for H63D allele was detected in 20.0% of cases and 21.4% of controls, whereas C282Y allele was detected neither among cases nor in controls.
  
  
  CONCLUSIONS
  The presence of the relatively high frequency of A1AT S and HFE H63D allele carriers in Egyptian cases of HCV liver cirrhosis suggest the necessity to implement routine molecular analysis of these genes for detection of risk genotypes among affected families.
authors.affiliation: Manosura University Children Hospital, Mansoura, Egypt. settin@mans.edu.eg
authors.forename: Ahmad
authors.initials: A
authors.lastname: Settin
authors.forename: Mahmoud
authors.initials: M
authors.lastname: El-Bendary
authors.forename: Rabab
authors.initials: R
authors.lastname: Abo-Al-Kassem
authors.forename: Rizk
authors.initials: R
authors.lastname: El Baz
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004534:Egypt / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D019698:Hepatitis C, Chronic / Q000150:complications*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; 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