Programmed cell death‐1 3′‐untranslated region polymorphism is associated with spontaneous clearance of hepatitis B virus infection

Abstract

Hepatitis B virus (HBV)-specific CD8+ T cells play an important role in the clearance of HBV infection. Programmed cell death-1 (PD-1), an immunosuppressive molecule that regulates T-cell activation and peripheral immune tolerance, is increasingly shown to influence the outcome of HBV infection. rs10204525, a single-nucleotide polymorphism in the 3'-untranslated region (3'-UTR) of PD-1, has been associated with susceptibility and disease progression of chronic HBV infection in far-eastern patients. The aim of our study was to assess the impact of rs10204525 variation on HBV infection in Moroccan patients. A total of 236 patients with chronic HBV infection and 134 individuals with spontaneous HBV resolution were genotyped using a Taqman assay. In addition, PD-1 mRNA expression in peripheral blood nuclear cells was determined by quantitative reverse-transcription polymerase chain reaction. We found that the AA genotype is protective (odds ratio, 0.43; 95% confidence interval, 0.19 to 0.97; P = 0.038) against HBV infection. Interestingly, PD-1 messenger RNA (mRNA) expression analysis has revealed that chronic HBV carriers with GG and GA displayed higher levels of PD-1 mRNA compared with corresponding genotypes in resolved subjects (P = 0.031 and 0.014, respectively). Our data suggest that Mediterranean HBV-infected patients carrying PD-1 GG and GA genotypes at rs10204525 have high PD-1 mRNA expression and may be more prone to installation of chronicity.

Association between PDCD1 gene polymorphisms and psoriasis susceptibility in the Chinese population

“…Mediterranean HBV‐infected patients carrying GG and GA genotypes for PD1.6 displayed high PD‐1 mRNA expression. 27 Differently, a significant higher percentage of PD1 protein expression on T cells was observed for PD1.6 AA genotype as compared to GG genotype in the Chinese Han population. 28 Despite the discrepancy, regulation of PDCD1 gene expression by PD1.6 polymorphism is likely to happen.…”

“… 26 The AA genotype of PD1.6 was reported to be protective against HBV infection in Moroccan patients. 27 In contrast, the AA genotype of PD1.6 significantly increased the risk of persistent HCV infection in the Chinese Han population aged ≤56 years, while the G allele of PD1.6 was shown to clear HCV spontaneously and play protective roles in females infected with HCV. 28 To our knowledge, the present study is the first to reveal that the PDCD1 polymorphism is associated with the risk of psoriasis.…”

PD-1/PD-L1 Immuno-Mediated Therapy in NAFLD: Advantages and Obstacles in the Treatment of Advanced Disease

“…Polymorphisms in the PD-1 gene have been associated with an increased risk of various types of cancers and some of them alter protein expression and function [ 31 ]. The PD-1 rs10204525 C > T and rs7421861 A > G variants boost PD-1 expression and have been associated with increased risk of esophageal cancer in Asian individuals [ 32 ]. Furthermore, Kaplan-Meier survival curves showed that higher PD-1 gene expression contributed to worse survival of esophageal cancer patients [ 32 ].…”

Genetics, Immunity and Nutrition Boost the Switching from NASH to HCC

“…Polymorphisms in the PDCD-1 gene have been associated with an increased risk of various types of cancers and some of them alter protein expression and function [ 55 ]. The PDCD-1 rs10204525 C > T is located in the 3′ UTR, it increases PD-1 expression and has been associated with persistence in HBV infection [ 57 ]. The rs7421861 A > G in PDCD-1 gene is localized in the intron 1, where there are several alternative splicing sites [ 24 ].…”