Characterization of Genetic Polymorphism of Glycine N-Methyltransferase Gene in Hepatocellular Carcinoma.

Previously, we reported that glycine N-methyltransferase (GNMT) expression levels were diminished in human liver cancer. Herein, the polymorphisms of GNMT in 5 hepatocellular carcinoma (HCC) and 2 hepatoblastoma (HBL) cell lines were analyzed. In the HCC cell lines, 4/5 had homozygous genotypes in all the GNMT polymorphism markers expect PLC/PRF/5 which had a G/A genotype of SNP3. Among 6 GNMT polymorphism markers, HA22T/VGH had 3 homo and 3 heterozygous genotypes. In contrast, both Huh 6 and Hep G2 HBL cell lines had heterozygous genotypes in most of their GNMT polymorphism markers. The INS/DEL genotypes of GNMT in peripheral blood mononuclear cells of 308 HCC patients were analyzed. The data indicate that the rates of homozygous insertion (INS/INS), heterozygous (INS/DEL), and homozygous deletion (DEL/DEL) genotypes were 11.59%, 48.19% and 40.11%, respectively. When the SNP1 genotype was analyzed, we found that the genotype rates of T/T, T/C, and C/C in HCC patients were 1.30%, 25.65% and 73.05%, respectively. The frequency distribution of both INS/DEL and SNP1 genotypes in HCC patients was not statistically different from those of the 304 normal controls. When the interaction between GNMT genotypes and HBV infection were analyzed, the data showed that among patients without HBV infection, those with C/C genotype had a 1.55-fold higher risk of developing HCC. Further studies in the interaction between GNMT and risk factors for HCC besides HBV are needed. [ABSTRACT FROM AUTHOR]