title: Genetic variants associated with the progression of hepatocellular carcinoma in hepatitis C Egyptian patients.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) associated to infection with hepatitis C virus (HCV) has become the fastest-rising cause of cancer-related deaths. Genetic variations may play an important role in the development of HCC in HCV patients. Ghrelin exerts anti-inflammatory, antifibrotic and hepatoprotective effects on chronically injured hepatic tissues. Ghrelin gene shows several single nucleotide polymorphisms (SNPs) including -604G/A, Arg51Gln, and Leu72Met. Hemochromatosis gene (HFE) mutations namely C282Y and H63D may cause hepatic iron overload, thus increasing the risk of HCC in HCV patients.
  
  
  OBJECTIVE
  To investigate the association of progression of HCC with ghrelin and HFE gene polymorphisms in HCV Egyptian patients.
  
  
  METHODS
  Seventy-nine chronic HCV patients (thirty-nine developed HCC and forty did not), and forty healthy control subjects were included in the study. The polymorphisms were evaluated by PCR/RFLP analysis, and related protein levels were measured by either ELISA or colorimetric assays.
  
  
  RESULTS
  The three tested SNPs on ghrelin gene were detected in the studied groups, only one SNP (Arg51Gln) showed significantly higher GA, AA genotypes and A allele frequencies in hepatitis C patients who developed HCC than in hepatitis C patients without HCC and controls. Of the two mutations studied on HFE gene only H63D heterozygous allele was detected, and its frequency did not statistically differ among studied groups.
  
  
  CONCLUSIONS
  Our results suggest that A allele at position 346 of the ghrelin gene is associated with susceptibility to HCC in hepatitis C patients.
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Tarek Kamal
authors.initials: TK
authors.lastname: Motawi
authors.forename: Olfat Gamil
authors.initials: OG
authors.lastname: Shaker
authors.forename: Manal Fouad
authors.initials: MF
authors.lastname: Ismail
authors.forename: Noha Hussein
authors.initials: NH
authors.lastname: Sayed
mesh_terms: D000328:Adult; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D017931:DNA Primers; D018450:Disease Progression; D004534:Egypt; D005260:Female; D014644:Genetic Variation; D006526:Hepatitis C / Q000150:complications / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers
keywords: ALT; AST; Alanine aminotransferase; Aspartate aminotransferase; Bcl I; Bsr I; C/EBP-α; CCAAT/enhancer-binding protein alpha; Dra I; EDTA; ELISA; Enzyme-linked immunosorbent assay; Ethylenediaminetetra acetic acid; Fe(2)-TF; Genetic variants; Ghrelin; HCC; HCV; HCV hepatitis; HFE; HH; Hepatitis C virus; Hepatocellular carcinoma; Hepcidin; Hereditary hemochromatosis; IL-1β; IL-6; IL-8; Interleukin-1 beta; Interleukin-6; Interleukin-8; Iron–transferrin complex; MCP-1; MHC-1; Major histocompatibility complex class 1; Monocyte chemoattractant protein-1; PCR; Polymerase chain reaction; Pro-Arg; Pro-Gln; Proline-arginine; Proline-glycine; RFLP; ROS; Reactive oxygen species; Restriction enzyme from Bacillus caldolyticus; Restriction enzyme from Deinococcus radiophilus; Restriction enzyme from Rhodopseudomonas sphaeroides; Restriction enzyme from Streptomyces achromogenes; Restriction fragment length polymorphism; Rsa I; STAT-3; Sac I; Signal transducer and activator of transcription-3; TFR1; TFR2; TNBS; TNF-α; Transferrin receptor 1; Transferrin receptor 2; Trinitrobenzene sulfonic acid; Tumor necrosis factor alpha; restriction enzyme from Bacillus stearothermophilus