GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers.

ABSTRACT: Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV-related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV-positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV-positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR?=?1.30, P?=?1.13×10?¹?) and rs455804 (GRIK1) on 21q21.3 (OR?=?0.84, P?=?1.86×10??), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR?=?1.25, P?=?1.71×10??; rs455804: OR?=?0.84, P?=?6.92×10?³). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV-related HCC, suggesting the involvement of glutamate signaling in the development of HBV-related HCC.

SUBMITTER: Li S 

PROVIDER: S-EPMC3395595 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature