Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection.
Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection.
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DOI：
10.1111/jvh.12899
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发表时间：
2018-08
影响因子：
2.5
通讯作者：
Wang BB
中科院分区：
文献类型：
--
作者：
Wang S;Wang J;Fan MJ;Li TY;Pan H;Wang X;Liu HK;Lin QF;Zhang JG;Guan LP;Zhernakova DV;O'Brien SJ;Feng ZR;Chang L;Dai EH;Lu JH;Xi HL;Zeng Z;Yu YY;Wang BB
B肝炎表面抗原（HBsAg）和B肝炎表面抗原抗体（抗-HBs）共存的机制仍有争议。为了确定与这种异常临床现象相关的宿主遗传因素，在中国汉族人群中进行了两阶段研究。在第一阶段，我们进行了一个病例对照（1：1）年龄，性别匹配的研究101例HBsAg和抗-HBs和102例对照HBsAg阴性和抗-HBs阳性使用全外显子测序。在第二个验证阶段，我们直接测序OAS 3基因上的16个外显子，在两个依赖的队列中，48例病例和200例对照。虽然在第一阶段，对101例病例和102例对照的58,563个多态性变异进行的全基因组关联研究没有发现显著的位点，（P值≤ 0.05/58563），两个位点均未达到保守的全基因组显著性阈值（P值≤ 5e-08），基于基因的负荷分析显示OAS 3基因罕见变异与HBsAg和抗-HBs共存相关。（P值=4.127e-06 ≤ 0.05/6994）。从21例病例和3例对照中筛选出16种罕见变异。在第二个验证阶段，确定了一个新的不同罕见变异的病例。对149例病例组和302例对照组的Fisher精确检验显示，病例组的罕见编码序列突变发生率高于对照组[P值=7.299e-09，OR=17.27，95%CI（5.01-58.72）]。OAS 3基因编码蛋白的罕见变异与中国汉族慢性HBV感染者HBsAg和抗-HBs共存相关
The underlying mechanism of coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antigen antibody (anti-HBs) is still controversial. To identify the host genetic factors related to this unusual clinical phenomenon, a two-staged study was conducted in the Chinese Han population. In the first stage, we performed a case-control (1:1) age, gender matched study of 101 cases with concurrent HBsAg and anti-HBs and 102 controls with negative HBsAg and positive anti-HBs using whole exome sequencing. In the second validation stage, we directly sequence the 16 exons on the OAS3 gene in two dependent cohorts of 48 cases and 200 controls. Although in the first stage, a genome-wide association study of 58,563 polymorphism variants in 101 cases and 102 controls found no significant loci (P-value ≤ 0.05/58563), and neither locus achieved a conservative genome-wide significance threshold (P-value ≤ 5e-08), gene-based burden analysis showed that OAS3 gene rare variants were associated with the coexistence of HBsAg and anti-HBs. (P-value =4.127e-06 ≤ 0.05/6994). 16 rare variants were screened out from 21 cases and 3 controls. In the second validation stage, one case with a new different rare variant was identified. Fisher's exact test of all 149 cases and 302 controls showed that the rare coding-sequence mutations were more frequent in cases versus controls [P-value=7.299e-09, OR=17.27, 95% CI (5.01-58.72)]. Protein-coding rare variations on the OAS3 gene are associated with the coexistence of HBsAg and anti-HBs in patients with chronic HBV infection in Chinese Han population.
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