Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection

S. Wang; J. Wang; M. J. Fan; T. Y. Li; H. Pan; X. Wang; H. K. Liu; Q. F. Lin; J. G. Zhang; L. P. Guan; D. V. Zhernakova; S. J. O’Brien; Z. R. Feng; L. Chang; E. H. Dai; J. H. Lu; H. L. Xi; Z. Zeng; Y. Y. Yu; B. B. Wang; Stephen James O'Brien

doi:10.1111/jvh.12899

Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection

S. Wang
, J. Wang
, M. J. Fan
, T. Y. Li
, H. Pan
, X. Wang
, H. K. Liu
, Q. F. Lin
, J. G. Zhang
, L. P. Guan
, D. V. Zhernakova
, S. J. O’Brien
, Z. R. Feng
, L. Chang
, E. H. Dai
, J. H. Lu
, H. L. Xi
, Z. Zeng
, Y. Y. Yu
, B. B. Wang

Stephen James O'Brien

Department of Biological Sciences

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

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.

Original language	American English
Pages (from-to)	904-910
Number of pages	7
Journal	Journal of Viral Hepatitis
Volume	25
Issue number	8
DOIs	https://doi.org/10.1111/jvh.12899
State	Published - Aug 1 2018

Bibliographical note

Funding

The project has been supported by ZZ research grant from International Science & Technology Cooperation Program of China (No. 2014DFR31200), National Natural Science Foundation of China (No. 30671855) and federal funds from the National Cancer Institute, National Institutes of Health, USA, under Contract No. N01-CO-12400. The content of this publication does not necessarily reflect the views of policies of the Department of the Health and Human Service, nor does the mention of trade names, commercial products or organizations imply endorsement by the United States Government. International Science & Technology Cooperation Program of China, Grant/Award Number: No. 2014DFR31200; federal funds from the National Cancer Institute, National Institutes of Health, USA, Grant/Award Number: No. N01-CO-12400; National Natural Science Foundation of China, Grant/ Award Number: No.30671855

Funders	Funder number
International Science & Technology Cooperation Program of China	2014DFR31200
National Institutes of Health
National Cancer Institute	N01-CO-12400
National Cancer Institute
National Natural Science Foundation of China	30671855
National Natural Science Foundation of China

ASJC Scopus Subject Areas

Infectious Diseases
Virology
Hepatology

Keywords

OAS3
coexistence of HBsAg and anti-HBs
rare variants
whole exome sequencing
Genome-Wide Association Study
Humans
Middle Aged
Male
Sequence Analysis, DNA
2',5'-Oligoadenylate Synthetase/genetics
Genetic Variation
Ethnicity
Hepatitis B Surface Antigens/blood
Hepatitis B, Chronic/genetics
Adult
Female
Hepatitis B Antibodies/blood
Asian People

Disciplines

Genetics and Genomics
Life Sciences

Access to Document

10.1111/jvh.12899License: Unspecified

https://doi.org/10.1111/jvh.12899

Cite this

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., ... O'Brien, S. J. (2018). Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection. Journal of Viral Hepatitis, 25(8), 904-910. https://doi.org/10.1111/jvh.12899

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 & O'Brien, SJ 2018, 'Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection', Journal of Viral Hepatitis, vol. 25, no. 8, pp. 904-910. https://doi.org/10.1111/jvh.12899

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title = "Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection",

abstract = " 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{\textquoteright}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.",

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author = "S. Wang and J. Wang and Fan, \{M. J.\} and Li, \{T. Y.\} and H. Pan and X. Wang and Liu, \{H. K.\} and Lin, \{Q. F.\} and Zhang, \{J. G.\} and Guan, \{L. P.\} and Zhernakova, \{D. V.\} and O{\textquoteright}Brien, \{S. J.\} and Feng, \{Z. R.\} and L. Chang and Dai, \{E. H.\} and Lu, \{J. H.\} and Xi, \{H. L.\} and Z. Zeng and Yu, \{Y. Y.\} and Wang, \{B. B.\} and O'Brien, \{Stephen James\}",

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T1 - Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection

AU - Wang, S.

AU - Wang, J.

AU - Fan, M. J.

AU - Li, T. Y.

AU - Pan, H.

AU - Wang, X.

AU - Liu, H. K.

AU - Lin, Q. F.

AU - Zhang, J. G.

AU - Guan, L. P.

AU - Zhernakova, D. V.

AU - O’Brien, S. J.

AU - Feng, Z. R.

AU - Chang, L.

AU - Dai, E. H.

AU - Lu, J. H.

AU - Xi, H. L.

AU - Zeng, Z.

AU - Yu, Y. Y.

AU - Wang, B. B.

AU - O'Brien, Stephen James

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

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KW - coexistence of HBsAg and anti-HBs

KW - rare variants

KW - whole exome sequencing

KW - Genome-Wide Association Study

KW - Humans

KW - Middle Aged

KW - Male

KW - Sequence Analysis, DNA

KW - 2',5'-Oligoadenylate Synthetase/genetics

KW - Genetic Variation

KW - Ethnicity

KW - Hepatitis B Surface Antigens/blood

KW - Hepatitis B, Chronic/genetics

KW - Adult

KW - Female

KW - Hepatitis B Antibodies/blood

KW - Asian People

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UR - https://doi.org/10.1111/jvh.12899

UR - https://www.scopus.com/pages/publications/85050810279

UR - https://www.scopus.com/pages/publications/85050810279#tab=citedBy

U2 - 10.1111/jvh.12899

DO - 10.1111/jvh.12899

M3 - Article

C2 - 29582521

SN - 1352-0504

VL - 25

SP - 904

EP - 910

JO - Journal of Viral Hepatitis

JF - Journal of Viral Hepatitis

IS - 8

ER -

Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection

Abstract

Bibliographical note

Funding

ASJC Scopus Subject Areas

Keywords

Disciplines

Access to Document

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