Since the findings are not consistent in different study cohorts [18], [20], the association of these HLA-DP SNPs with HBV disease activity remains unclear. In the present study, we primarily aimed to investigate the association of 3 HLA-DP SNPs, namely rs3077, rs9277378 and rs3128917, with chronicity of HBV infection 17-AAG side effects in the Chinese population in Hong Kong. In addition, we studied the association of these SNPs with hepatitis B disease activity. This will extend our understanding of the association between HLA-DP variations and HBV infection and may provide some evidences to explain the widely different prevalence of chronic HBV in different ethnic groups in the world. Patients and Methods Patients The present study recruited 500 chronic HBV carriers (hepatitis B surface antigen [HBsAg]-positive for more than 6 months) who had been followed up in our liver clinics in the Queen Mary Hospital, Hong Kong.
Upon their first and/or follow up visits, these HBV carriers had given verbal informed consent for the storage of blood samples for further studies. We have also recruited 706 consecutive HBsAg-negative control subjects who have donated blood at the Hong Kong Red Cross Blood Transfusion Service, and they all had given verbal informed consent during blood donation for the storage of blood samples. Data were analyzed anonymously for the 706 HBsAg-negative blood donors. Approval has been obtained from the Institution Review Board, Queen Mary Hospital, The University of Hong Kong, for retrieving archived samples for this study.
Among the 706 HBsAg-negative subjects, 202 had previous history of hepatitis B vaccination and were excluded from the subsequent analysis. All study patients/subjects are Chinese, and all blood samples were collected during the period January 2010 to March 2011. All subjects were tested negative for hepatitis C virus and human immunodeficiency virus by the Procleix Ultrio Assay (Novartis Diagnostics, Emeryville, CA). Of the 504 non-vaccinated control subjects, 259 had HBV natural clearance (HBV clearance group), denoted by the presence of detectable anti-HBc by the Elecsys assay (Roche Diagnostics, Basel, Switzerland). The remaining 245 subjects (non-HBV infected group) were negative for both HBsAg and anti-HBc. Longitudinal clinical data, including alanine aminotransferase (ALT) and HBV DNA measurements, were obtained from the 500 HBV carriers.
Inactive asymptomatic HBV carriers were defined by HBV DNA levels <2,000 IU/ml and persistently normal ALT (<58 U/L for male and <36 U/L for female) for least 12 months. Genotyping Assays Three SNPs within chromosome 6, namely rs3077 (in the 3�� untranslated region of the HLA-DPA1 gene), rs9277378 and rs3128917 (inside and near the HLA-DPB1 gene, respectively), were studied (Figure Cilengitide 1).