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Chronic hepatitis B virus (HBV) infection is a challenging global health problem. To identify genetic loci involved in chronic HBV infection, we designed a three-phase genome-wide association study in Han Chinese populations. The discovery phase included 951 HBV carriers (cases) and 937 individuals who had naturally cleared HBV infection (controls) and was followed by independent replications with a total of 2,248 cases and 3,051 controls and additional replications with 1,982 HBV carriers and 2,622 controls from the general population. We identified two new loci associated with chronic HBV infection: rs3130542 at 6p21.33 (near HLA-C, odds ratio (OR) = 1.33, P = 9.49 × 10−14) and rs4821116 at 22q11.21 (in UBE2L3, OR = 0.82, P = 1.71 × 10−12). Additionally, we replicated the previously identified associations of HLA-DP and HLA-DQ variants at 6p21.32 with chronic HBV infection. These findings highlight the importance of HLA-C and UBE2L3 in the clearance of HBV infection in addition to HLA-DP and HLA-DQ. [ABSTRACT FROM AUTHOR]

Background: The interleukin-23 receptor (IL-23R) plays an important role in the T-helper 17 cell-mediated inflammatory process and is also involved in tumor immune surveillance, which may be linked to carcinogenesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). In this study, we hypothesized that potentially functional genetic variants of the IL-23R gene may modify HCC risk.Methods: We genotyped two single-nucleotide polymorphisms (SNPs) of IL-23R, rs6682925 and rs1884444, in a case-control study of 837 HCC cases, 899 HBV surface antigen (HBsAg)-positive controls, and 743 HBsAg-negative controls. A reporter gene assay was performed to evaluate the functional relevance of the rs6682925 SNP located at the promoter region of the IL-23R gene.Results: We found that the two SNPs were associated with the risk of HCC when compared with both the HBsAg-positive and -negative controls. When compared with all controls, IL-23R rs6682925 and rs1884444 both increased the HCC risk in a recessive genetic model [rs6682925 CC vs. TT/TC: odds ratio (OR) 1.35, 95 % confidence interval (CI) 1.07-1.70; rs1884444 GG vs. TT/TG: OR 1.36, 95 % CI 1.05-1.77]. Furthermore, the variant C allele of rs6682925 in the promoter region of IL-23R was associated with increased reporter gene activity.Conclusions: These findings indicate that genetic variants in IL-23R may contribute to HCC development. [ABSTRACT FROM AUTHOR]

Abstract  Matrix metallopeptidase-9 (MMP-9) plays a pivotal role in vascular remodeling and development of atherosclerotic lesion. The potentially functional MMP-9 polymorphisms may contribute to the susceptibility of coronary artery disease (CAD). A case–control study composed of 762 CAD cases and 555 CAD-free controls was conducted in a Chinese population to investigate the association between the MMP-9 −1562 C>T, R279Q, P574R and R668Q polymorphisms and CAD risk. It was found that the variant genotypes of R279Q, P574R and R668Q were associated with a non-significant decreased risk of CAD when compared with their wild-type genotypes, respectively, Furthermore, compared with those without any variant genotypes for these four nonsynonymouse loci, individuals carrying all four variant genotypes (−1562 CT/TT, 279 RQ/QQ, 574 PR/RR and 668 RQ/QQ) had a 51% decreased risk of CAD (adjusted OR = 0.49; 95% CI = 0.26–0.95, P = 0.033). Although no significant main effects were observed for MMP-9 −1562 C>T locus on CAD risk, variant genotypes of −1562 C>T were associated with a 2.53 increased risk of CAD in subjects with diabetes mellitus (DM) (95% CI = 1.18–5.45, P = 0.018). In CAD cases, variant genotypes of −1562 C>T were associated with a significantly increased risk of MI (adjusted OR, 1.48, 95% CI, 1.01–2.20, P = 0.048). These findings suggest that MMP-9 R279Q, P574R and R668Q may have combined effect in the occurrence of CAD and −1562 CT/TT genotypes may contribute to CAD in diabetics and MI in CAD patients. [ABSTRACT FROM AUTHOR]