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Analysis of HLA alleles in Japanese patients with cirrhosis due to chronic hepatitis C
Author(s) -
HIGASHI YOICHIRO,
KAMIKAWAJI NOBUHIRO,
SUKO HIRONOBU,
ANDO MASAYUKI
Publication year - 1996
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.1996.tb00069.x
Subject(s) - typing , human leukocyte antigen , allele , medicine , hepatitis c virus , serology , immunology , cirrhosis , virology , hepatitis c , liver disease , allele frequency , linkage disequilibrium , restriction fragment length polymorphism , population , virus , genotype , antigen , genetics , gastroenterology , biology , haplotype , gene , antibody , environmental health
Hepatitis C virus (HCV) leads to chronic liver disease in at least 50–60% of infected people and approximately 40–50% of these patients will go on to develop cirrhosis due to chronic hepatitis C (HCV‐C). The pathogenic mechanisms that result in HCV‐C are unknown. Sixty Japanese patients with HCV‐C were examined for HLA‐A, B, C and DR alleles by serologic typing and for HLA‐DQB1 alleles by DNA typing using the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method. As the control population, 293 healthy un‐related Japanese were used. The frequencies of HLA‐B61 , Cw3, DR4, DQB1*0401 and DQB1*0402 were increased, while those of HLA‐DR9, DQB1*0301 and DQB1*0303 were decreased in the patients. The co‐ordinate increase in the frequency of HLA‐DR4, DQB1*0401 or 0402 and decrease in the frequency of DR9 or DQB1*0303 were suggestive of a strong linkage disequilibrium between HLA‐DR4 and DQB1*0401 or 0402 and between HLA‐DR9 and DQB1*0303 , respectively. From the odds ratio (OR) analysis, the combinations of HLA‐Cw3+DR4‐DQB1*0401 or 0402 , or HLA‐B61+DR4‐DQB1*0401 or 0402 increased the risk for developing HCV‐C when compared to each HLA allele alone. This suggested an additive effect for these classes I and II HLA allele combinations in HCV‐C. In contrast, HLA‐DR9‐DQB1*0303 and DQB1*0301 may confer resistance to this disease. These results suggest the existence of HLA ‐linked susceptibility genes to HCV‐C.