Identified OAS3 gene variants associated with coexistence of HBsAg and anti‐HBs in chronic HBV infection. Issue 8 (29th May 2018)

• Record Type: Journal Article
• Authors: Wang, S.; Wang, J.; Fan, M‐J.; Li, T‐Y.; Pan, H.; Wang, X.; Liu, H‐K.; Lin, Q‐F.; Zhang, J‐G.; Guan, L‐P.; Zhernakova, D. V.; O'Brien, S. J.; Feng, Z‐R.; Chang, L.; Dai, E‐H.; Lu, J‐H.; Xi, H‐L.; Zeng, Z.; Yu, Y‐Y.; Wang, B‐B.
• Is Part Of: Journal of viral hepatitis. Volume 25:Issue 8(2018)
• Page Start: 904
• Page End: 910
• Publication Date: 2018-05-29
• Subjects: coexistence of HBsAg and anti‐HBs -- OAS3 -- rare variants -- whole exome sequencing; Hepatitis, Viral -- Periodicals; Hepatitis, Viral, Animal; Hepatitis, Viral, Human; 616.3623
• DOI: 10.1111/jvh.12899
• Languages: English
• ISSNs: 1352-0504

Abstract

Summary: 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‐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 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 ≤ .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). 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 OAS3 gene are associated with the coexistence of HBsAg and anti‐HBs in patients with chronic HBV infection in Chinese Han population.