Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus.
The human leukocyte antigen is a crucial genetic factor that initiates or regulates immune response by presenting foreign or self antigens to T lymphocytes. The aim of this study was to investigate whether HLA polymorphism is associated with the onset or progression of liver injury in chronic hepatitis C virus (HCV) infection. We determined HLA class I antigens and class II alleles in 130 hepatitis C virus (HCV)-infected patients (33 carriers with persistently normal alanine transaminase [ALT] values and 97 patients with chronic liver disease [CLD]). HLA class I (A, B) was typed serologically, and class II (DRB1, DQB1) was typed by means of polymerase chain reaction-restriction fragment length polymorphism methods. The frequencies of DRB1*0405 and DQB1*0401 were higher in HCV-infected patients than in uninfected subjects. Among HCV-infected patients, the frequencies of B54, DRB1*0405, and DQB1*0401 were significantly higher in patients with CLD than in those carriers with persistently normal ALT values, whereas DRB1*1302, DRB1*1101, and DQB1*0604 were more frequently found in carriers with persistently normal ALT values than in patients with CLD. From extended haplotype analyses, in carriers with B54-DRB1*0405-DQB1*0401 haplotype, the risk of having liver injury was 13.2 times greater than in carriers with DRB1*0405-DQB1*0401 but without B54 [P = 0.0015, Haldane odds ratio = 13.2 (95% confidence interval, 1.7-103.8)]. In contrast, carriers with B44-DRB1*1302-DQB1*0604 had a 12.7-fold lower relative risk of developing liver injury compared to those with the haplotype containing B44 but not DRB1*1302-DQB1*0604 [P = 0.0076, Haldane odds ratio = 0.079 (0.009-0.695)]. Our findings show that extended haplotypes including class I B54 are closely associated with the progression of liver injury, whereas extended haplotypes including class II DRB1*1302-DQB1*0604 are associated with low hepatitis activity in chronic HCV infection.
Kuzushita
N
N
First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
Hayashi
N
N
Moribe
T
T
Katayama
K
K
Kanto
T
T
Nakatani
S
S
Kaneshige
T
T
Tatsumi
T
T
Ito
A
A
Mochizuki
K
K
Sasaki
Y
Y
Kasahara
A
A
Hori
M
M
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000483:Alleles; D002908:Chronic Disease; D005260:Female; D005787:Gene Frequency; D006680:HLA Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012016:Reference Values
D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; D000410:Alanine Transaminase