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Genetic variants of programmed cell death 1 are associated with HBV infection and liver disease progression
Nghiem Xuan Hoan 1 2 3 , Pham Thi Minh Huyen 4 5 , Mai Thanh Binh 6 7 , Ngo Tat Trung 8 , Dao Phuong Giang 6 , Bui Thuy Linh 6 , Dang Thi Ngoc Dung 9 , Srinivas Reddy Pallerla 10 , Peter G Kremsner 6 10 , Thirumalaisamy P Velavan 6 10 , Mai Hong Bang 6 7 , Le Huu Song 4 6
Affiliations
Affiliations
1
Department of Blood-Borne Infectious Diseases, Institute of Clinical Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam. [email protected].
2
Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam. [email protected].
3
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany. [email protected].
4
Department of Blood-Borne Infectious Diseases, Institute of Clinical Infectious Diseases, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam.
5
Department of Biochemistry, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam.
6
Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.
7
Faculty of Gastroenterology, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam.
8
Centre for Genetic Consultation and Cancer Screening, 108 Institute of Clinical Medical and Pharmaceutical Sciences, Hanoi, Vietnam.
9
Hanoi Medical University, Hanoi, Vietnam.
10
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
PMID: 33833369 DOI: 10.1038/s41598-021-87537-9
Abstract
The inhibitory effects of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) modulates T-cell depletion. T-cell depletion is one of the key mechanisms of hepatitis B virus (HBV) persistence, in particular liver disease progression and the development of hepatocellular carcinoma (HCC). This case-control study aimed to understand the significance of PD-1 polymorphisms (PD-1.5 and PD-1.9) association with HBV infection risk and HBV-induced liver disease progression. Genotyping of PD-1.5 and PD-1.9 variants was performed by direct Sanger sequencing in 682 HBV-infected patients including chronic hepatitis (CHB, n = 193), liver cirrhosis (LC, n = 183), hepatocellular carcinoma (HCC, n = 306) and 283 healthy controls (HC). To analyze the association of PD-1 variants with liver disease progression, a binary logistic regression, adjusted for age and gender, was performed using different genetic models. The PD-1.9 T allele and PD-1.9 TT genotype are significantly associated with increased risk of LC, HCC, and LC + HCC. The frequencies of PD-1.5 TT genotype and PD-1.5 T allele are significantly higher in HCC compared to LC patients. The haplotype CT (PD-1.5 C and PD-1.9 T) was significantly associated with increased risk of LC, HCC, and LC + HCC. In addition, the TC (PD-1.5 T and PD-1.9 C) haplotype was associated with the risk of HCC compared to non-HCC. The PD-1.5 CC, PD-1.9 TT, genotype, and the CC (PD-1.5 C and PD-1.9) haplotype are associated with unfavorable laboratory parameters in chronic hepatitis B patients. PD-1.5 and PD1.9 are useful prognostic predictors for HBV infection risk and liver disease progression.
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