7 The same group also performed a second GWAS, with an increased sample size of 458 Japanese persistent HBV infection cases and 2,056 controls for additional GWA scan, and they found
such an association with another two SNPs (rs2856718 and rs7453920) in HLA-DQ.8 However, in these two GWAS studies, the data on HBV exposure of controls were unknown, which may have introduced information bias in the results. PI3K inhibitor To further test the association of HLA-DP/DQ variants with risk of both HBV clearance and HCC development, we genotyped these four SNPs in 1,300 HBV-positive HCC patients, 1,344 chronic HBV carriers, and 1,344 subjects with HBV natural clearance in Southeast Han Chinese populations. CD, cluster of differentiation; χ2, chi-square test; CI, 95% confidence
interval; GWA, genome-wide association; GWAS, genome-wide association study; anti-HBc, antibody against hepatitis B core antigen; anti-HBs, antibody against hepatitis B surface antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; anti-HCV, HCV antibody; HCC, hepatocellular carcinoma; HLA, human leukocyte antigen; LD, linkage disequilibrium; OR, odds ratio; SNPs, single-nucleotide polymorphisms; WT, wild type. This study was approved by the Institutional Review Board of Nanjing Medical LY2606368 University (Nanjing, China). Briefly, HCC patients were consecutively recruited between January 2006 and December 2010 at the Nantong Tumor Hospital (Nantong, China), Qidong Liver Cancer Institute (Qidong, 上海皓元 China), and the First Affiliated Hospital of Nanjing
Medical University without restrictions of age and sex. The diagnosis of HCC was confirmed by a pathological examination and/or alpha-fetoprotein elevation (>400 ng/mL) combined with imaging examination (i.e., magnetic resonance imaging and/or computerized tomography). Because HCV infection is rare in Chinese populations, we excluded patients with HCC with HCV infection. As a result, 1,300 HBV-positive HCC cases consented to participate in the study and provided blood samples. Two groups of controls were used in the current study: one was the HBV persistent carrier group and the other was a group of subjects with HBV natural clearance. Overall, the controls from two cities in Jiangsu Province (9,720 subjects from Changzhou and 48,422 subjects from Zhangjiagang) were screened for the HBV/HCV (hepatitis C virus) markers in 2004 and 2009. All participants were self-reported Han Chinese and more than 30 years old. HBV persistent carriers were those who were positive for both HBsAg and antibody against hepatitis B core antigen (anti-HBc), but negative for HCV antibody (anti-HCV); subjects with HBV natural clearances were those who were negative for HBsAg and anti-HCV, but positive for both antibodies against hepatitis B surface antigen (anti-HBs) and anti-HBc.
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