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

Abstract

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.

Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus

“…Consequently, we found higher frequencies of DRB1*0405 and DQB1*0401 in HCVinfected patients than in normal subjects. By contrast, Tibbs et al 30 reported that frequencies of DQB1*0302 and DQA1*03 in HCV-infected patients were significantly lower than in normal controls. Therefore, the possibility exists that some HLA class II DR or DQ alleles may influence the chronicity of HCV infection.…”

Viral clearance in hepatitis C (1b) infection: Relationship with human leukocyte antigen class II in a homogeneous population

“…However, this may be explained by accounting for differences in the phenotype frequency (pf) of DQB1*0401 alleles in the Japanese and Irish populations, where n is equal to the number of subjects possessing the particular phenotype, and P is equal to the total number of subjects in the sample population; (pf ϭ n/P); pf(Japan) ϭ 0.28, n ϭ 260, P ϭ 916, and pf(Ireland) ϭ 0, n ϭ 0, P ϭ 93. Tibbs et al 34 reported a correlation between HLA DQB1*0302 (p corr ϭ .04) and clearance of HCV infection compared with controls. This contrasts with the findings from our study group for the DQB1*0302 allele and clearance of HCV (Table 3).…”

Chronic viral hepatitis and the human genome

“…3 Most studies to date of HBV and HCV have employed this method of study, but difficulties involved in designing such studies include an inappropriate control group (detailed later) or a small number of study participants. [14][15][16][17][18][19][20][21] The control group in most of the viral hepatitis studies is from the general population [22][23][24][25][26][27][28] or from blood or bone marrow donors, [29][30][31] which can lead to a misclassification bias because some of these individuals may not have been exposed to the virus. In such cases, true associations may be missed because unexposed subjects capable of becoming infected are included as controls.…”

“…Several studies have attempted to examine susceptibility to HCV infection by comparing HLA alleles in individuals who are anti-HCV-positive with either the general population or with people who are anti-HCVnegative (Table 4). [25][26][27][28][29]31,[63][64][65] Because the assumption cannot be made that the general population has been exposed to HCV, true associations may be missed by this experimental design. In addition, identification of individuals who have been exposed to HCV but remain seronegative is difficult.…”

“…The haplotype DRB1*1601-DQB1*0502 was more frequent in the HCVnegative thalassemic controls relative to the anti-HCV-positive individuals. Several other studies have identified associations between class I and/or class II alleles and HCV infection, [25][26][27][28][29] but class I typing was performed using serological techniques, and controls always involved individuals who were unlikely to have been exposed to the virus. In general, among these studies, many different HLA associations were identified, but a few supported data from studies of HCV clearance and progression.…”