Identified OAS OAS 3 gene variants associated with coexistence of HB HB sAg and anti‐ HB HB s in chronic HBV HBV infection

摘要

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.