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Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source
Author(s) -
McKiernan Susan M.,
Hagan Richard,
Curry Michael,
McDonald George S. A.,
Kelly Alan,
Nolan Niamh,
Walsh Anne,
Hegarty John,
Lawlor Emer,
Kelleher Dermot
Publication year - 2004
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.20261
Subject(s) - allele , immunology , human leukocyte antigen , hepatitis c virus , biology , odds ratio , genotype , virology , major histocompatibility complex , haplotype , typing , viral load , hepatitis b virus , medicine , virus , antigen , genetics , gene
The role of cytotoxic T lymphocyte responses, restricted by human leukocyte antigen (HLA) class I alleles, is recognized as highly significant in the successful clearance of hepatitis C virus (HCV). The frequency of class I alleles in females inoculated with HCV genotype 1b from a single source was examined for an association with outcome. Class I typing was performed using polymerase chain reaction sequence‐specific primers in 227 female subjects: 141 had chronic infection and 86 had viral clearance. Statistical analysis included χ 2 testing and multiple logistic regression analysis. A*03, B*27, and Cw*01 occurred more frequently in those with viral clearance (39.5%, 14%, and 9.3%, respectively) compared with those with chronic infection (19.1%, 2.1%, and 1.4%, respectively; P ≤ .005). B*08 occurred more often in those with chronic infection compared with viral clearance (39.7% vs. 19.8%; P = .002). In combination with previously reported class II allele associations, over 75% that successfully eliminate HCV carry either A*03, DRB1*0101, or *0401, compared with only 37% of those with chronic infection ( P < .0001). The haplotypes A*03‐B*07‐DRB1*15‐DQB1*0602 and A*02‐B*27‐Cw*01‐DRB1*0101‐DQB1*0501 are associated with viral clearance ( P = .004 and .01, respectively). By multiple logistic regression analysis, the alleles A*03, B*27, DRB1*0101, *0401, and *15 are associated with viral clearance, and B*27 has the strongest association (odds ratio [OR] 7.99). The haplotype A*01‐B*08‐Cw*07‐DRB1*03011‐DQB1*0201 is associated with chronic infection ( P = .002), being independent for DQB1*0201 (OR 0.27). In conclusion , certain class I alleles are associated with outcome in this homogenous cohort. More significantly, either HLA‐A*03, ‐DRB1*0101, or ‐*0401 are carried by an overwhelming majority of those subjects who successfully clear HCV. (H EPATOLOGY 2004;40:108–114.)