Multi-clustering study on the association between human leukocyte antigen-DP-DQ and hepatitis B virus-related hepatocellular carcinoma and cirrhosis in Viet Nam  

作　　者：Thuy Thu Nguyen Tu Cam Ho Huong Thi Thu Bui Van-Khanh Tran Tue Trong Nguyen 

机构地区：[1]Center for Gene and Protein Research,Hanoi Medical University,Hanoi 116177,Viet Nam [2]Institute of Virology,TUM School of Medicine,Technical University of Munich,Munich 81675,Germany [3]Department of Biochemistry,Thai Nguyen University of Medicine and Pharmacy,Thai Nguyen 251540,Viet Nam [4]Medical Technology Department,Hanoi Medical University,Hanoi 116177,Viet Nam [5]Clinical Laboratory,Hanoi Medical University Hospital,Hanoi 116177,Viet Nam

出　　处：《World Journal of Gastroenterology》2024年第46期4880-4903,共24页世界胃肠病学杂志（英文）

基　　金：Supported by National Foundation for Science and Technology Development(NAFOSTED)-Ministry of Science and Technology,Viet Nam,No.108.02-2019.307.

摘　　要：BACKGROUND Human leukocyte antigen(HLA)class II molecules are cell surface receptor proteins found on antigen-presenting cells.Polymorphisms and mutations in the HLA gene can affect the immune system and the progression of hepatitis B.AIM To study the relation between rs2856718 of HLA-DQ,rs3077,and rs9277535 of HLA-DP,hepatitis B virus(HBV)-related cirrhosis,and hepatocellular carcinoma(HCC).METHODS In this case-control study,the genotypes of these single nucleotide polymorphisms(SNPs)were screened in 315 healthy controls,471 chronic hepatitis B patients,250 patients with HBV-related liver cirrhosis,and 251 patients with HCC using TaqMan real-time PCR.We conducted Hardy-Weinberg equilibrium and linkage disequilibrium tests on the genotype distributions of rs2856718,rs3077,and rs9277535 before hierarchical clustering analysis to build the complex interaction between the markers in each patient group.RESULTS The physical distance separating these SNPs was 29816 kB with the disequilibrium(D’)values ranging from 0.07 to 0.34.The close linkage between rs3077 and rs9277535 was attributed to a distance of 21 kB.The D’value decreased from moderate in the healthy control group(D’=0.50,P<0.05)to weak in the hepatic disease group(D’<0.3,P<0.05).In a combination of the three variants rs2856718,rs3077,and rs9277535,the A allele decreased hepatic disease risk[A-A-A haplotype,risk ratio(RR)=0.44(0.14;1.37),P<0.05].The G allele had the opposite effect[G-A/G-G haplotype,RR=1.12(1.02;1.23),P<0.05].In liver cancer cases,the A-A-A/G haplotype increased the risk of HCC by 1.58(P<0.05).CONCLUSION Rs9277535 affects liver fibrosis progression due to HBV infection,while rs3077 is associated with a risk of HBVrelated HCC.The link between rs2856718,rs3077,and rs9277535 and disease risk was determined using a multiclustering analysis.

关 键 词：Human leukocyte antigen Multi-clustering study Hepatitis B virus Hepatocellular carcinoma CIRRHOSIS 

分 类 号：R575.2[医药卫生—消化系统] R735.7[医药卫生—内科学]