The genetic polymorphism of CYP7A1 in Fujian Han HBV infected patients

Objective The study aims to investigate the associationbetweencholesterol 7α-hydroxylase (CYP7A1) gene polymorphism and different clinical outcomes after Hepatitis B virus (HBV) infection in Fujian Han population and lay a foundation for understanding the mechanisms of genesis and development of HBV-related diseases. Methods Case-control study was conducted.586 patients of HBV persistent infection without antiviral therapy and 225 HBV rehabilitation patients(35-55 years old) were collected from May 2015 to June 2016 in the Liverish Center of First Clinical College of Fujian Medical University.The group of HBV persistent infection without antiviral therapy included 246 patients with chronic hepatitis B, 177 patients with hepatitis B-related cirrhosis, and 163 patients with hepatitis B-related liver cancer.The rs3824260, rs4738687and rs8192871 loci of CYP7A1 gene were detected by improved multiple ligase detection reaction (iMLDR). Logistic regression analysis and chi-square test were used to analyze the genotyping results. Results Three SNPs (single nucleotide polymorphisms) of CYP7A1 gene were selected and compared between HBV persistent infection group and HBV rehabilitation group and between chronic hepatitis B subgroup, liver cirrhosis subgroup and liver cancer subgroup. After adjustment for factors including age andgender, there was no significant difference in the distribution of rs3824260 genotype among the groups(χ2=1.565, P=0.459), however, the frequency of allele C in HBV rehabilitation group was significantly higher than in HBV persistent in fectiongroup for men(χ2=4.365, P=0.037), whereas the frequency of rs3824260 CC and CT was more likely to be observed in liver cancer group than in non-liver cancer group (chronic hepatitis B subgroup and liver cirrhosis subgroup) for women (χ2=5.768, P=0.012; χ2=10.130, P=0.001). The frequency of rs4738687 GG genotype was more likely to be observed in non-liver cancer group than in liver cancer group (χ2=4.403, P=0.041; χ2=6.940, P=0.009). The results of gender stratification showed that there were significant differences in the distribution of rs4738687 among the HBV persistent infection groups for men(χ2=10.697, P=0.030), however, there was no significant difference in the distribution of rs4738687 among the HBV persistent infection groups for women(χ2=4.627, P=0.329), and there was no significant difference in the distribution of genotype frequency and allele frequency among all groups(χ2=0.489, P=0.792). There was no significant difference after sex stratification either(χ2=1.282, P=0.526; χ2=1.565, P=0.465). Conclusions These findings suggested that CYP7A1 gene polymorphism was related todifferent clinical outcomes in Fujian Han population. The rs3824260 mutation had a certain gender preference and the mutation allele was detected in a higher proportion in male patients. Male HBV patients with rs3824260 C allele had more chance of switching to rehabilitation. The rs4738687 was likely to be related to the occurrence of liver cancer in Fujian Han population, and GG genotype may delay the occurrence and development of liver cancer especially in the male group. The rs8192871 was not found to be related to the different clinical outcomes of HBV infection.(Chin J Lab Med, 2018, 41: 155-164) Key words: Hepatitis B virus; Polymorphism single nucleotide; Cholesterol 7-alpha-Hydroxylase