length polymorphism analysis. In addition, although there In the search for factors which may influence susceptiare several reports from the Mayo Clinic, these are all based bility to and outcome from chronic hepatitis C virus on a single cohort of patients and their investigations were (HCV) infection, few studies have considered the influconfined to the HLA DR and DQB genes and did not include ence of host genes. In the present investigation we have the DQA1 or DPB1 genes. The purpose of the present study performed HLA DRB1, DQA1, DQB1, and DPB1 genotypwas to address the question of HLA-encoded susceptibility in ing on 104 northern European patients with chronic a large series of patients with chronic HCV infection, using HCV infection and 177 racially and geographically medium to high resolution molecular genotyping techniques, matched controls. Three HLA class II alleles, DRB1*0403, and to extend current investigations to the HLA DQA1 and DQA1*03, and DQB1*0302 were present at a significantly DPB1 genes. In addition we sought correlation between HLA lower frequency in patients compared with controls class II alleles and disease severity. (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 PATIENTS AND METHODS significant after correction for multiple testing (pc ร
0.038, and pc ร
0.046, respectively). No further HLA asso-Patients and Controls. A cohort of 104 well documented northern
ciations with chronic HCV infection were observed and European white patients referred to the HCV clinic at King's College there was no correlation between stage of disease and Hospital were studied (Table 1). All had detectable hepatitis C anti- HLA genotype. These data provide the first suggestion body in serum and 99 of the patients also had HCV-RNA detected by polymerase chain reaction (Amplicore, Roche, Welwyn Garden that susceptibility to chronic HCV infection may be in-City, England). Liver biopsies were performed on 89 of the patients; fluenced by the hosts' HLA DQ alleles. (HEPATOLOGY 19 were cirrhotic, 21 classified as chronic active hepatitis, and 48 had included for haplotype analysis only.
The HLA class II DRB1, DQA1, DQB1, and DPB1 alleles were determined using polymerase chain reaction amplification and a se-Abbreviations: HCV, hepatitis C virus; RR, relative risk. ries of sequence and allele specific oligonucleotide probes, as de-From the