Institute of Liver Disease, Huazhong University of Science and Technology, Wuhan, China.
Viral Immunol. 2011 Oct;24(5):397-402. doi: 10.1089/vim.2011.0027.
Host genetics play a vital role in determining clinical outcomes of hepatitis B virus (HBV) infection. To identify novel susceptibility loci to HBV progression, we carried out a genome-wide association study with DNA pooling. This study assessed the relationship between 8 highly-ranked SNPs selected from our DNA pool and disease progression of HBV infection in two independent case-control studies. The first population included 628 asymptomatic HBV carriers (AsC) and 1729 progressed HBV carriers recruited from Hubei Province in south China. The second population was composed of 226 AsC and 215 progressed HBV carriers recruited from Shandong Province in north China. Of the 8 SNPs, variant rs11866328 (G/T), located in the glutamate receptor ionotropic N-methyl D-aspartate 2A (GRIN2A) gene, was replicated and had significant associations with disease progression of HBV infection in the DNA pooling stage both in the Hubei (OR 1.65; 95% CI 1.34,2.02; p=1.96 × 10(-6); additive model), and in the Shandong (OR 1.73; 95% CI 1.14,2.65; p=1.00×10(-2); additive model) population. Polymorphism rs11866328 in the GRIN2A gene might be a genetic variant underlying the susceptibility of HBV carriers to disease progression.
宿主遗传学在确定乙型肝炎病毒 (HBV) 感染的临床结果方面起着至关重要的作用。为了确定与 HBV 进展相关的新的易感基因座，我们进行了一项基于 DNA 池的全基因组关联研究。这项研究评估了从我们的 DNA 池中选择的 8 个高度排名的单核苷酸多态性（SNPs）与中国南方湖北省的 628 名无症状 HBV 携带者（AsC）和 1729 名进展 HBV 携带者以及中国北方山东省的 226 名 AsC 和 215 名进展 HBV 携带者之间的疾病进展关系。在这 8 个 SNP 中，位于谷氨酸受体离子型 N-甲基-D-天冬氨酸 2A（GRIN2A）基因中的变体 rs11866328（G/T）在 DNA 池阶段的复制和与 HBV 感染疾病进展的关联具有显著意义，在湖北（OR 1.65；95%CI 1.34，2.02；p=1.96×10(-6)；加性模型）和山东（OR 1.73；95%CI 1.14，2.65；p=1.00×10(-2)；加性模型）人群中均如此。GRIN2A 基因中的多态性 rs11866328 可能是导致 HBV 携带者易患疾病进展的遗传变异。
