Abstract
Background:The relationship of leptin (LEP) and polymorphism of leptin receptor (LEPR) were studied in patients with hepatocellular carcinoma (HCC) and compared with those with liver cirrhosis to find out the extent of the risk of LEPR on patients with HCC. Methods:Serum LEP level and LEPR Q223R gene polymorphism were determined in 300 patients with liver disease categorized equally into five groups’ healthy volunteers, patients with hepatitis C (HCV), patients with non-alcoholic steatohepatitis (NASH), liver cirrhosis and HCC. LEPR gene was amplified by polymerase chain reaction (PCR) then digested by the MSP1 restriction enzyme. Results:The isolated 212 bp of LEPR was sequenced. The serum LEP level was reduced in patients with cirrhotic and HCC. Serum LEP level had negatively correlated with both tumor grade and size in HCC patients. The data obtained from restriction fragment length polymorphismPCR and sequencing revealed the existence of a novel synonymous Q223R single nucleotide polymorphism (SNP) in exon 223 of LEPR gene (1137101). LEPR Gln223Arg, GG and GA genotypes were found in all studied groups. LEPR Gln223Arg, AA genotype was found in NASH, HCC, and control. LEPR Gln223Arg GA genotype is associated with some patients with HCC. Conclusion:GA genotype of LEPR Gln223Arg may be regarded as a probable genetic risk factor for Egyptian patients with HCC.
Highlights
Liver cancer is one of the most dangerous types of cancer and occurs as a result of chronic liver disease and hepatic fibrosis resulting from hepatitis B and C and chronic liver diseases (El-Zayadi et al, 2005)
This study aimed to assess between the level of the LEP hormone and leptin receptor (LEPR) Gln223Arg in Egyptian patients with liver cirrhosis that leads to hepatocellular carcinoma (HCC)
We have found an increase in the incidence of HCC with an increased prevalence of HCV and less prevalence of Virus B as risk factors (El-Zayadi et al, 2005)
Summary
Liver cancer is one of the most dangerous types of cancer and occurs as a result of chronic liver disease and hepatic fibrosis resulting from hepatitis B and C and chronic liver diseases (El-Zayadi et al, 2005). The pathogenesis of this association is not fully understood It seems that there is a relationship between adipocytokines, such as LEP, and HCC but the molecular mechanisms have not been clarified yet (Caldwell et al, 2004). Methods: Serum LEP level and LEPR Q223R gene polymorphism were determined in 300 patients with liver disease categorized into five groups’ healthy volunteers, patients with hepatitis C (HCV), patients with non-alcoholic steatohepatitis (NASH), liver cirrhosis and HCC. The serum LEP level was reduced in patients with cirrhotic and HCC. LEPR Gln223Arg GA genotype is associated with some patients with HCC. Conclusion: GA genotype of LEPR Gln223Arg may be regarded as a probable genetic risk factor for Egyptian patients with HCC
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