Single nucleotide polymorphism in the promoter region of human alpha-fetoprotein (AFP) gene and its significance in hepatocellular carcinoma (HCC)

BackgroundVariations of serum AFP levels in HCC patients and cell lines are likely due to the differential activity of enhancer/silencer elements that control AFP. To understand the potential mechanism underlying the differential expression of AFP, we have examined the sequence of the AFP promoter in HCC.MethodsDirect DNA sequencing was carried out to sequence 980 bp of AFP promoter of DNA samples isolated from 83 HCC patients.ResultsThree novel SNPs in the promoter region of the AFP gene, which have not been previously reported, were found at positions −330, −401 and −692. The level of serum AFP was significantly higher in HCC patients with the CT genotype of 330 SNP or the AG genotype of the 401 SNP. The genotype of CG in 692 SNP was also associated with a significant elevated level of serum AFP, and further this genotype appeared to be associated with the high risk of HCC development. 401 SNP and 692 SNP were located at the positions of known binding sites for transcription factors that have a role in the production of AFP and the growth of tumors.ConclusionsThe novel polymorphisms identified in the promoter region of the AFP gene may be pathologically significant in HCC.