Background and purpose: Membrane cofactor protein CD46 protects host cells from complement-dependent cytotoxicity and may be a potential molecular marker for hepatocellular carcinoma (HCC). This study aimed to investigate the correlation between the gene expression of CD46 with the genetic variation of CD46 promoter and the risk of HCC. Methods: The difference in CD46 expression between HCC tissues and normal liver tissues was analyzed by gene expression profiling interactive analysis (GEPIA) online website. From 2011 to 2015

240 HCC patients were confirmed by pathological diagnosis in Tangshan Gongren Hospital

North China University of Science and Technology and Tangshan People’s Hospital

North China University of Science and Technology

and 500 healthy people enrolled as the control group in the same period. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to detect genotype frequencies and allele frequencies between two groups. The relationship between the genetic variation of CD46 rs1970530 and the risk of HCC was evaluated. Results: The expression of CD46 was significantly different between HCC tissues and normal tissues (P0.05). Unconditional logistic regression analysis indicated the difference in CD46 rs1970530 genotype carrying at least one G allele was statistically significant between the case group and the control group (OR=0.666

95% CI: 0.448-0.990

P0.05)

and there was also a significant difference in the frequency of the allele G (OR=0.689

95% CI: 0.478-0.994

P0.05). The stratification analysis showed that CD46 rs1970530 genotype carrying at least one G allele could reduce the risk of HCC in the advanced age group (60 years) (P=0.048) and men (P=0.023)

however

there was no difference in women and younger age groups between the HCC and the healthy control (≤60 years) (P0.05). Smoking stratification analysis indicated that there was no significant correlation between rs1970530 mutation and HCC susceptibility (P0.05). Conclusion: The high gene expression of CD46 in HCC and the genetic variation of CD46 rs1970530 affect the risk of HCC.