Association of a functional intronic polymorphism rs735396 in HNF1A gene with the susceptibility to hepatocellular carcinoma in Han Chinese population

Background: Single nucleotide polymorphism rs735396 located in HNF1A gene was highly associated with the levels of glycan groups which changed during carcinogenesis and progression of HCC after HBV infection. In present study, we investigated if rs735396 are associated with the susceptibility to HBV infection and HBV-related HCC. Methods: Totally 568 HBV-related HCC patients, 110 HBV carriers without HCC and 380 healthy controls in Han Chinese population were recruited and genotyped using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. To evaluate the effects of rs735396 polymorphisms on transcription of HNF1A, the luciferase activity for allelotype A or G was detected in HepG2.2.15 cells. Results: The genotype distribution and allelic frequencies were significantly different between HBV-related HCC patients and healthy controls (P < 0.05). Also, compared with genotype GG, genotypes AA+GA are connected with a higher risk of HBV-related HCC (Odds Ratio = 1.908; 95% Confidence Interval = 1.390-2.619, P < 0.001). Moreover, luciferase activity for allelotype A was significantly lower than that of allelotype G (P = 0.036). Conclusion: Taken together, we demonstrated that the variation of HNF1A rs735396 influences host susceptibility to HBV-related HCC by altering transcriptional activity of HNF1A.