Evidence that the HLA DQA1^*03 allele confers protection from chronic HCV-infection in northern European Caucasoids.

In the search for factors which may influence susceptibility to and outcome from chronic hepatitis C virus (HCV) infection, few studies have considered the influence of host genes. In the present investigation we have performed HLA DRB1, DQA1, DQB1, and DPB1 genotyping on 104 northern European patients with chronic HCV infection and 177 racially and geographically matched controls. Three HLA class II alleles, DRB1*0403, DQA1*03, and DQB1*0302 were present at a significantly lower frequency in patients compared with controls (4.9% vs. 13%, 20.7% vs. 41.2%, and 11.4% vs. 30.5%, respectively) though only two DQB1*0302 and DQA1*03 were significant after correction for multiple testing (pc = 0.038, and pc = 0.046, respectively). No further HLA associations with chronic HCV infection were observed and there was no correlation between stage of disease and HLA genotype. These data provide the first suggestion that susceptibility to chronic HCV infection may be influenced by the hosts' HLA DQ alleles.

[1]  A. Czaja,et al.  HLA-DQ associations in type 1 autoimmune hepatitis. , 1995, Mayo Clinic proceedings.

[2]  J. She,et al.  Differential prevalence of HLA class II DQB1 but not DRB1 alleles in Caucasian patients with chronic hepatitis C , 1995 .

[3]  H C Thomas,et al.  Association between an MHC class II allele and clearance of hepatitis B virus in the Gambia. , 1995, The New England journal of medicine.

[4]  N. Hayashi,et al.  Influence of viral quasispecies on effectiveness of interferon therapy in chronic hepatitis C patients , 1994, Hepatology.

[5]  G. Pape,et al.  T cell recognition of hepatitis B and C viral antigens , 1994, European journal of clinical investigation.

[6]  D. Doherty,et al.  The molecular genetics of autoimmune liver disease , 1994, Hepatology.

[7]  M. Manns,et al.  Immunogenetics of chronic liver diseases. , 1994, Gastroenterology.

[8]  J. Hoofnagle,et al.  Classification of chronic hepatitis: Diagnosis, grading and staging , 1994, Hepatology.

[9]  K. Chayama,et al.  Factors predictive of response to interferon‐α therapy in hepatitis C virus infection , 1994, Hepatology.

[10]  Roger Williams,et al.  Allelic sequence variation in the HLA class II genes and proteins in patients with autoimmune hepatitis , 1994, Hepatology.

[11]  M. Urdea,et al.  Hepatitis C viremia in chronic liver disease: Relationship to interferon‐α or corticosteroid treatment , 1994, Hepatology.

[12]  Roger Williams,et al.  Virus‐induced autoimmunity in hepatitis C virus infections: A rare event , 1994, Journal of medical virology.

[13]  N. Mcintyre,et al.  Hepatitis C virus genotypes: An investigation of type‐specific differences in geographic origin and disease , 1994, Hepatology.

[14]  S. Gordon,et al.  The pathology of hepatitis C as a function of mode of transmission: Blood transfusion vs. Intravenous drug use , 1993, Hepatology.

[15]  A. Czaja,et al.  Genetic predispositions for the immunological features of chronic active hepatitis , 1993, Hepatology.

[16]  Nick Crofts,et al.  Hepatitis C virus infection among a cohort of Victorian injecting drug users , 1993, The Medical journal of Australia.

[17]  McFarlane Ig.  Hepatitis C and alcoholic liver disease. , 1993 .

[18]  G. Davis,et al.  Significance of serum hepatitis C virus RNA levels in chronic hepatitis C , 1993, The Lancet.

[19]  M A Gerber,et al.  The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. , 1992, The New England journal of medicine.

[20]  S. Mishiro,et al.  The degree of variability in the amino terminal region of the E2/NS1 protein of hepatitis C virus correlates with responsiveness to interferon therapy in viremic patients , 1992, Hepatology.

[21]  Motohiro Shibata,et al.  Detection of hepatitis C virus by polymerase chain reaction and response to interferon‐α therapy: Relationship to genotypes of hepatitis C virus , 1992, Hepatology.

[22]  R. Vaughan,et al.  HLA DQA, DQB, and DRB genotyping by oligonucleotide analysis: distribution of alleles and haplotypes in British caucasoids. , 1992, Human immunology.

[23]  O. Olerup,et al.  HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours: an alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation. , 1992, Tissue antigens.

[24]  M. Sheehy.  HLA and Insulin-Dependent Diabetes. A protective perspective , 1992, Diabetes.

[25]  R. Vries.  1991 MACK FORSTER AWARD LECTURE REVIEW , 1992 .

[26]  Andrew J. McMichael,et al.  Common West African HLA antigens are associated with protection from severe malaria , 1991, Nature.

[27]  G. Nepom.  A Unified Hypothesis for the Complex Genetics of HLA Associations With IDDM , 1990, Diabetes.

[28]  J. Goudsmit,et al.  Prevalence, incidence, and risk factors of hepatitis C virus infection among drug users in Amsterdam. , 1990, The Journal of infectious diseases.

[29]  F. Alvarez,et al.  Chronic active hepatitis associated with antiliver/kidney microsome antibody type 1: A second type of “autoimmune” hepatitis , 1987, Hepatology.

[30]  B. Benacerraf.  Role of MHC gene products in immune regulation. , 1981, Science.

[31]  O. J. Dunn.  Multiple Comparisons among Means , 1961 .

[32]  O. J. Dunn.  Estimation of the Means of Dependent Variables , 1958 .

[33]  B. Woolf.  ON ESTIMATING THE RELATION BETWEEN BLOOD GROUP AND DISEASE , 1955, Annals of human genetics.

[34]  A. Czaja,et al.  Immunologic features and HLA associations in chronic viral hepatitis. , 1995, Gastroenterology.

[35]  N. Enomoto,et al.  Clinical backgrounds of the patients having different types of hepatitis C virus genomes. , 1992, Journal of hepatology.