MHC class II genes influence the susceptibility to chronic active hepatitis C.
OBJECTIVE
Chronic hepatitis C develops in more than 70% of hepatitis C virus infected subjects. Viral factors influence the disease course, but little is known about the importance of host factors.


METHODS
Frequencies of major histocompatibility complex (MHC) class I and class II antigens were analyzed in two groups of patients with chronic hepatitis C virus infection and in control subjects. MHC class I typing was done by standard microlymphocytotoxicity assays. DRB1 and DQA1 genotyping was done by PCR based typing methods.


RESULTS
DRB1*0301 was found in 26 of 75 patients with chronic hepatitis C virus infection (34.7%) and in 12 of 101 control subjects (11.9%) (relative risk 3.9; p < 0.001). Homozygosity for this allele appeared to confer a stronger risk. In contrast, DRB1*1301 was detected in three subjects with persistent infection (4.0%) compared to 21 control subjects (20.8%) (relative risk 0.2; p < 0.008). This allele was linked with DQA1*0103, which was found in 10 patients (13.3%) compared to 34 control subjects (33.7%) (relative risk 0.31; p < 0.003). An even stronger protective effect was provided by the presence of DRB1*1301 and DQA1*0103 (relative risk 0.08; p < 0.005). These findings were confirmed in a second group of chronic hepatitis C virus infected patients.


CONCLUSIONS
The MHC class II allele DRB1*0301 appears to predispose to progression to chronic active hepatitis C, whereas the class II alleles DRB1*1301 and DQA1*0103 appear to provide protection against chronic active infection with hepatitis C virus.
Höhler
T
T
Department of Internal Medicine, Johannes Gutenberg University Mainz, Germany.
Gerken
G
G
Notghi
A
A
Knolle
P
P
Lubjuhn
R
R
Taheri
H
H
Schneider
P M
PM
Meyer zum Büschenfelde
K H
KH
Rittner
C
C
D000483:Alleles; D000961:Antilymphocyte Serum / Q000032:analysis; D018450:Disease Progression; D004198:Disease Susceptibility / Q000276:immunology; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics / Q000502:physiology; D059848:HLA-DQ alpha-Chains; D006684:HLA-DR Antigens / Q000235:genetics / Q000502:physiology; D059811:HLA-DRB1 Chains; D006526:Hepatitis C / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D006521:Hepatitis, Chronic / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006720:Homozygote; D006801:Humans; D016133:Polymerase Chain Reaction; D012016:Reference Values
D000961:Antilymphocyte Serum; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II