Genetic variants associated with the progression of hepatocellular carcinoma in hepatitis C Egyptian patients

• Association of ghrelin Arg51Gln and susceptibility to HCC in HCV Egyptian patients.
• No association of Ghrelin − 604G/A or Leu72Met with HCC in HCV Egyptian patients.
• HFE C282Y or H63D not associated with HCC in HCV Egyptian patients.
• Suppressed hepcidin production in HCV patients may lead to iron overload.
• Metabolic disturbances may lead to elevated ghrelin level in HCV patients.

BackgroundHepatocellular 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.AimTo investigate the association of progression of HCC with ghrelin and HFE gene polymorphisms in HCV Egyptian patients.MethodsSeventy-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.ResultsThe 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.ConclusionOur results suggest that A allele at position 346 of the ghrelin gene is associated with susceptibility to HCC in hepatitis C patients.