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  • Original Article
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New genetic associations detected in a host response study to hepatitis B vaccine

Abstract

The immune response to hepatitis B vaccination differs greatly among individuals, with 5–10% of healthy people failing to produce protective levels of antibodies. Several factors have been implicated in determining this response, chiefly individual genetic variation and age. Aiming to identify genes involved in the response to hepatitis B vaccination, a two-stage investigation of 6091 single-nucleotide polymorphisms (SNPs) in 914 immune genes was performed in an Indonesian cohort of 981 individuals showing normal levels of anti-HBs versus 665 individuals displaying undetectable levels of anti-HBs 18 months after initial dose of the vaccine. Of 275 SNPs identified in the first stage (476 normal/372 nonresponders) with P<0.05, significant associations were replicated for 25 polymorphisms in 15 genes (503 normal/295 nonresponders). We validated previous findings (HLA-DRA, rs5000563, P-value combined=5.57 × 10−10; OR (95%CI)=0.61 (0.52–0.71)). In addition, we detected a new association outside of the human leukocyte antigen loci region that passed correction for multiple testing. This SNP is in the 3′ downstream region of FOXP1, a transcription factor involved in B-cell development (P-value combined=9.2 × 10−6; OR (95%CI)=1.38 (1.2–1.6)).These findings might help to understand the biological reasons behind vaccine failure and other aspects of variation in the immune responses of healthy individuals.

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Acknowledgements

We are grateful to our colleagues at the Genome Institute of Singapore, Heng Khai Koon and Jason Ong for genotyping, Boon Yeong Goh for sample management and Frans Verhoef for maintaining the GISSNP database. We also thank Dr Jan van Hattum, Jan and Annemarie van den Berg for their dedication and enthusiasm in arranging and performing all the vaccinations. Finally, we thank Dr Sangkot Marzuki, Dr Herawati Sudoyo and Dr David Mulyono of the Eijkman Institute for Molecular Biology in Jakarta, Indonesia, for their invaluable advice, insights and assistance with this project. This work was supported by funding from the Agency for Science & Technology and Research of Singapore (A*STAR) and the US Defense Advanced Research Projects Agency Contract Number W911QY-06-C-0085. FEMF was supported by a Dr Saal van Zwanenberg fellowship.

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Correspondence to S Davila or M Seielstad.

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Davila, S., Froeling, F., Tan, A. et al. New genetic associations detected in a host response study to hepatitis B vaccine. Genes Immun 11, 232–238 (2010). https://doi.org/10.1038/gene.2010.1

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