Linkage-distribution Analysis Of Polymorphisms Of PDCD1with HBV Infection Eradication/Persistence And Disease Prognosis

Objective:To clarify the suspected linkage between SNPs of programmed cell death1(PDCD1) gene and immunological viral clearance and histopathological injury and disease progression course and prognosis in patients with HBV infection.Methods:Case-controlled study was performed in297patients with persistent chronic HBV infections which included103asymptomatic carriers,114cases with chronic hepatitis B and80cases with severe chronic hepatitis B, and82cases who had had eradicated their previous HBV infection were served as control. Three PDCD1SNPs at positions rs36084323, rs2227981and rs2227982of both groups were analyzed by Mass ARRAY SNP MALDI-TOF mass spectrum (MALDI-TOF MS) and then the genotypic distribution was analyzed according the recorded clinical data of their viral eradication and degree of pathohistological injury and disease progression course according to their clinical data.Results:①PDCD1rs2227981C allele frequency was significantly higher in patients with chronic hepatitis B as compared with the control (p=0.03); and CC genotype frequency and C allele frequency of PDCD1rs2227982were less in patients with chronic hepatitis as compared with the control (P=0.01) indicating that CC gene carriers had less risk to become chronic hepatitis (OR=0.35,95%CI:0.16-0.77); ②The CC genotype and C allele of PDCD1rs2227981were significantly higher in chronic active hepatitis B (CAHB) as compared with the controls (P=0.02, P=0.01) indicating that the C allele might be risk factor for HBV infection persistence and chronic hepatitis B (OR=1.83,95%CI:1.15-2.93); while the CC genotype frequency and C allele frequency of PDCD1rs2227982in CAHB patients were less as compared with the controls (P=0.01, P=0.01) and indicating that the C allele might be a protective factor for HBV infection persistence and inducing chronic immunological injury (OR=0.57,95%CI:0.38-0.85);However, there were no significant difference was found between asymptomatic HBV carriers and chronic severe hepatitis B between the controls.③In our present study we didn’t find evident relationship between the SNPs of PDCDl and different disease status of HBV, nor significant correlation between the SNPs of PDCD1and the patients’serum HBV-DNA load. In addition, no statistically significant association was found between genotype distribution of SNPs of PDCD1and clinical disease courses and prognosis in patients suffered with chronic severe hepatitis B.Conclusion:①The C allele of PDCD1rs2227981and rs2227982mutations were associated with persistence of HBV infection and chronic immunological histopathological injury;②We didn’t find the relationship between the SNPs of PDCDl and different disease status of HBV infection in this present study, and nor evident correlation between the SNPs of PDCD1and the patients’ serum HBV DNA load. In addition, no statistically significant association was found between genotype distribution of SNPs of PDCD1and clinical course and prognosis in patients with chronic severe hepatitis B.③The results suggest that expand the sample size is essential to carry out linkage disequilibrium analysis and haplotype-based association analysis with other SNPs in genetic coding regions and non-coding regions.