Possible Relationship between Matrix Metalloproteinases Genotyping and Risk of Hepatocellular Carcinoma in HCV Infected Patients
Nermin Raafat *
Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Egypt.
Hala Mosaad
Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Egypt.
Wafaa Emam
Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Egypt.
Sherif M. Galal
Hepatology and Gastroenterology Department, Faculty of Medicine, Zagazig University, Egypt.
Khaled M. El-Gerby
Radio-diagnosis Department, Faculty of Medicine, Zagazig University, Egypt.
Yasser Elnaggar
Internal Medicine Department, Faculty of Medicine, Zagazig University, Egypt.
*Author to whom correspondence should be addressed.
Abstract
Background: The annual number of new cases of hepatocellular carcinoma (HCC) worldwide is over 1 million. In developing countries, the major cause of HCC is chronic hepatitis C virus (HCV) infection. Various studies have reported an association between functional gene polymorphism of matrix metalloproteinases (MMP) promoters and different cancers.
Rationale: This study examined the association between MMP1 -1607, MMP9-1562, MMP14-6727 and MMP14-6767 gene polymorphisms and risk of HCC in HCV infected patients.
Methods: The study enrolled 160 HCC patients, 91 with & 69 without chronic HCV infection, and 140 healthy subjects as control group. Genomic DNA was analysed for MMPs gene polymorphism using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) for MMP1 and MMP9 but real time PCR was used for MMP14 genotyping.
Results: MMP1-2G allele carriers had higher susceptibility of developing HCC in HCV infected patients. MMP9-1562 T/T genotype had high risk of developing HCC in HCV and non HCV related patients when compared to healthy controls. A significant lower risk for HCC was shown in individuals with MMP14-6767 G/A. The distribution frequency of MMP14-6767 G and MMP14-6727 C allele and homozygote genotype was significantly higher in HCC patients.
Conclusion: MMP-1 -1607 2G allele carriers would alter the risk of HCC under specific conditions such as chronic infection with HCV. People with MMP9-1562 T/T genotype are at risk of developing HCC. MMP14-6767 G and MMP14-6727 C allele carriers and homozygote genotype might contribute to the prediction of susceptibility and pathological development of HCC in HCV infected patients.
Keywords: Metalloproteinases, gene polymorphism, HCV, risk of HCC