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.
Aim: 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.
Conclusion: Our results suggest that A allele at position 346 of the ghrelin gene is associated with susceptibility to HCC in hepatitis C patients.
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.
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