Premium
Identified OAS 3 gene variants associated with coexistence of HB sAg and anti‐ HB s in chronic HBV infection
Author(s) -
Wang S.,
Wang J.,
Fan MJ.,
Li TY.,
Pan H.,
Wang X.,
Liu HK.,
Lin QF.,
Zhang JG.,
Guan LP.,
Zhernakova D. V.,
O’Brien S. J.,
Feng ZR.,
Chang L.,
Dai EH.,
Lu JH.,
Xi HL.,
Zeng Z.,
Yu YY.,
Wang BB.
Publication year - 2018
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12899
Subject(s) - gene , locus (genetics) , antigen , exon , population , microbiology and biotechnology , hbsag , biology , genetics , hepatitis b virus , medicine , virus , environmental health
Summary The underlying mechanism of coexistence of hepatitis B surface antigen ( HB sAg) and hepatitis B surface antigen antibody (anti‐ HB s) is still controversial. To identify the host genetic factors related to this unusual clinical phenomenon, a two‐stage study was conducted in the Chinese Han population. In the first stage, we performed a case‐control (1:1) age‐ and gender‐matched study of 101 cases with concurrent HB sAg and anti‐ HB s and 102 controls with negative HB sAg and positive anti‐ HB s using whole exome sequencing. In the second validation stage, we directly sequence the 16 exons on the OAS 3 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 ≤ .05/58563), and neither locus achieved a conservative genome‐wide significance threshold ( P ‐value ≤ 5e‐08), gene‐based burden analysis showed that OAS 3 gene rare variants were associated with the coexistence of HB sAg and anti‐ HB s. ( P ‐value = 4.127e‐06 ≤ 0.05/6994). A total of 16 rare variants were screened out from 21 cases and 3 controls. In the second validation stage, one case with a stop‐gained 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 vs controls ( P ‐value = 7.299e‐09, OR = 17.27, 95% CI [5.01‐58.72]). Protein‐coding rare variations on the OAS 3 gene are associated with the coexistence of HB sAg and anti‐ HB s in patients with chronic HBV infection in Chinese Han population.