程序性细胞死亡1的遗传变异与HBV感染和肝病进展有关

StephenW

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.

StephenW

程序性细胞死亡1的遗传变异与HBV感染和肝病进展有关
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
隶属关系
隶属关系

    1个
    越南河内市108临床医学和药学科学研究所临床传染病研究所血液传染病系。 [email protected]。
    2个
    越南河内越南-德国医学研究中心（VG-CARE）。 [email protected]。
    3
    德国蒂宾根大学蒂宾根大学热带医学研究所。 [email protected]。
    4
    越南河内市108临床医学和药学科学研究所临床传染病研究所血液传染病系。
    5
    越南河内108临床医学与药学学院生物化学系。
    6
    越南河内越南-德国医学研究中心（VG-CARE）。
    7
    越南河内108临床医学与药学学院胃肠病学系。
    8
    越南河内108临床医学和药学科学研究所遗传咨询和癌症筛查中心。
    9
    越南河内河内医科大学。
    10
    德国蒂宾根大学蒂宾根大学热带医学研究所。

    PMID：33833369 DOI：10.1038 / s41598-021-87537-9

抽象的

程序性细胞死亡1 /程序性细胞死亡配体1（PD-1 / PD-L1）的抑制作用调节T细胞耗竭。 T细胞耗竭是乙型肝炎病毒（HBV）持续存在的关键机制之一，尤其是肝脏疾病的进展和肝细胞癌（HCC）的发展。这项病例对照研究旨在了解PD-1多态性（PD-1.5和PD-1.9）与HBV感染风险和HBV诱发的肝病进展的关系。通过直接Sanger测序对682例HBV感染的患者进行PD-1.5和PD-1.9变体的基因分型，包括慢性肝炎（CHB，n = 193），肝硬化（LC，n = 183），肝细胞癌（HCC，n = 306）和283个健康对照（HC）。为了分析PD-1变异与肝病进展的关系，使用不同的遗传模型进行了年龄和性别调整的二元逻辑回归。 PD-1.9 T等位基因和PD-1.9 TT基因型与LC，HCC和LC + HCC风险增加显着相关。与LC患者相比，HCC中PD-1.5 TT基因型和PD-1.5 T等位基因的频率明显更高。单倍型CT（PD-1.5 C和PD-1.9 T）与LC，HCC和LC + HCC的风险增加显着相关。此外，与非HCC相比，TC（PD-1.5 T和PD-1.9 C）单倍型与HCC风险相关。在慢性乙型肝炎患者中，PD-1.5 CC，PD-1.9 TT，基因型和CC（PD-1.5 C和PD-1.9）单倍型与不利的实验室参数有关。 PD-1.5和PD1.9是预测HBV感染风险和肝病进展的有效预后指标。

StephenW

https://www.nature.com/articles/s41598-021-87537-9.pdf