Genome-Wide Association Study to Identify Genetic Factors Linked to HBV Reactivation Following Liver Transplantation in HBV-Infected Patients
Year: 2024
Type: article
Study design: Observational Study
Abstract: This study utilized a genome-wide association study (GWAS) to investigate the genetic variations linked to the risk of hepatitis B virus (HBV) reactivation in patients who have undergone liver transplantation (LT), aiming to enhance understanding and improve clinical outcomes. Genotyping performed on a selected patients from the Korean Organ Transplantation Registry (KOTRY) data using high-throughput platforms with the Axiom Korea Biobank array 1.1. The discovery cohort included 21 patients who experienced HBV reactivation (cases) and 888 patients without HBV reactivation (controls) following LT. The replication cohort consisted of 5 patients with HBV reactivation (cases) and 312 patients without HBV reactivation (controls) after LT. Additive logistic regression analysis was conducted using PLINK software ver 1.9, with adjustments for age and gender. The GWAS findings from the discovery cohort were validated using the replication cohort. The GWAS identified several single-nucleotide polymorphisms (SNPs) in the RGL1, CDCA7L, and AQP9 genes that were significantly linked to HBV reactivation after LT, with genome-wide significance thresholds set at p < 10−7. Down-regulation of RGL1 cDNAs was observed in primary duck hepatocytes infected with duck HBV. Overexpression of CDCA7L was found to promote hepatocellular carcinoma cell proliferation and colony formation, whereas knocking down CDCA7L inhibited these processes. Additionally, the absence of AQP9 triggered immune and inflammatory responses, leading to mild and scattered liver cell pyroptosis, accompanied by compensatory liver cell proliferation. This study provides critical insights into the genetic factors influencing HBV reactivation after LT, identifying significant associations with SNPs in RGL1, CDCA7L, and AQP9. These findings hold promise for developing predictive biomarkers and personalized management strategies to improve outcomes for HBV-infected LT recipients.
DOI: 10.3390/ijms26010259
Authors: Joonhong Park, Dong Yun Kim, Heon Yung Gee, Hee Chul Yu, Jae Do Yang, Shin Hwang, YoungRok Choi, Jae Geun Lee, Jinsoo Rhu, Donglak Choi, Young Kyoung You, Je Ho Ryu, Yang Won Nah, Bong-Wan Kim, Dong-Sik Kim, Jai Young Cho, The Korean Organ Transplantation Registry (KOTRY) Study Group
Institutions: Jeonbuk National University Hospital, Jeonbuk National University, Yonsei University, Korea University, Korea University Medical Center, Yonsei University Health System, Asan Medical Center, University of Ulsan, Seoul National University, Seoul National University Hospital, Samsung Medical Center, Sungkyunkwan University, Daegu Catholic University, Daegu Catholic University Medical Center, Catholic University of Korea, Pusan National University Yangsan Hospital, Ulsan University Hospital, Ajou University, Seoul National University Bundang Hospital
Language: English
Topic: Hepatitis B Virus Studies
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,296
Funders: Seoul National University Bundang Hospital, Catholic University of Daegu, Pusan National University, Seoul National University, University of Ulsan, Yonsei University, Ajou University, Korea University, Sungkyunkwan University, Catholic University of Korea, Seoul National University Hospital, Jeonbuk National University, Samsung, College of Medicine, Seoul National University, Korea National Institute of Health, Yonsei University College of Medicine, Ulsan University Hospital, College of Medicine, Catholic University of Korea
OpenAlex ID: W4405943364