Upregulation of Single Nucleotide Polymorphism of PD-1 Gene (rs10204525) in Chronic Hepatitis B Patients

Abstract

Background: Programmed death-1 (PD-1) is major inhibitory molecule that reduces T cell activation. PD-1 and their polymorphisms have separately been shown to be associated with hepatitis B virus (HBV) infection. Therefore, we aimed to investigate the association of PD1 polymorphisms with potential of chronic hepatitis B infection in Iranian population to do a Case-Control study. Methods: In this study HBV DNA, and PD-1 mRNA, were extracted from 60 patients with chronic hepatitis B and 60 healthy blood donors as control. HBV Viral Load, polymorphism genotype of the two groups and level expression of PD1 gene were evaluated using Real time PCR method. Results: Age mean of the control group was 40.7 ± 3.7 and 35.86 ± 11.18 year's old age for the case group. The GG allele between the two groups had the same frequency (73.3% in CHB group and 80% in healthy group). The GA allele in patients with hepatitis B (20%) was most frequent. There was a significant association between the GA allele and chronic hepatitis B infection. There was no significant relationship between the ages of the subjects with SNPrs10204525. Also, the expression of PD-1 mRNA was higher in people with hepatitis B than in healthy group. Conclusion: The results of this study showed that there is a significant relationship between the presence of rs10204525 polymorphisms in the PD-1 gene in patients with chronic hepatitis B infection and the association between the GA allele and chronic hepatitis B can be linked.

A PDCD1 Role in the Genetic Predisposition to NAFLD-HCC?

“…A number of SNPs have been identified that may alter the expression and function of PD-1, with reports linking these to autoimmune disease [ 59 ], but also immunosuppressive conditions. PDCD1 rs10204525 C > T is located at the 3′UTR, increasing PD-1 expression and reportedly promoting dysfunctional T cell responses and persistence in HBV infection [ 26 , 27 , 28 , 29 , 30 , 31 , 33 , 60 ]. The promotion of an immunosuppressive phenotype by PDCD1 rs10204525 C > T may also contribute to tumour development but has not as yet been characterised.…”

“…Here, in the hope of enhancing our understanding of NAFLD-HCC in a clinically translatable fashion, we have explored SNPs in a number of candidate HCC immunoregulatory genes, in addition to those in PNPLA3 and TM6SF2 , in patients with NAFLD and NAFLD-HCC. The SNPs selected were based on previous reports and included rs2596542 in Major Histocompatibility Complex class I polypeptide related sequence A ( MICA ) [ 19 ], rs187115 in Cluster of differentiation 44 ( CD44 ) [ 20 , 21 , 22 ], as well as rs7421861 and rs10204525 in programmed cell death-1 ( PDCD1 ) which encodes PD-1 [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. PDCD1 rs10204525 C < T is common in Asian populations, with functional implications for patients with HBV.…”

PD-1 and NFATc1 as promising immunotherapy for SLE patients

“…USA). The β-Globin primer (Housekeeping) was designed according to Mosaferi et al [25] and PD-1 primer was designed according to Ghorbani et al, [26], while NFATc1 primer is specially designed for this study by using (Primer 3) program, as shown in the table (1). Extraction of RNA TRIzolTM Reagent's protocol (Thermo Scientific, USA) were followed to isolate RNA from the samples.…”