Abstract:
:Vaccination against hepatitis B virus is an effective and routine practice that can prevent infection. However, 5-10% of healthy adults fail to produce protective levels of antibody against the hepatitis B vaccination. It has been reported that host genetic variants might affect the immune response to hepatitis B vaccination. Here, we reported a genome-wide association study in a Chinese Han population consisting of 108 primary high-responders and 77 booster non-responders to hepatitis B vaccination using the Illumina HumanOmniExpress Beadchip. We identified 21 SNPs at 6p21.32 were significantly associated with non-response to booster hepatitis B vaccination (P-value <1 × 10(-6)). The most significant SNP in the region was rs477515, located ∼12 kb upstream of the HLA-DRB1 gene. Its P-value (4.81 × 10(-8)) exceeded the Bonferroni-corrected genome-wide significance threshold. Four tagging SNPs (rs477515, rs28366298, rs3763316 and rs13204672) that capture genetic information of these 21 SNPs were validated in three additional Chinese Han populations, consisting of 1336 primary high-responders and 420 primary non-responders. The four SNPs continued to show significant associations with non-response to hepatitis B vaccination (P-combined = 3.98 × 10(-13)- 1.42 × 10(-8)). Further analysis showed that the rs477515 was independently associated with non-response to hepatitis B vaccination with correction for other three SNPs in our GWAS and the known hepatitis B vaccine immunity associated SNP in previous GWAS. Our findings suggest that the rs477515 was an independent marker associated with non-response to hepatitis B vaccination and HLA-DR region might be a critical susceptibility locus of hepatitis B vaccine-induced immunity.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Pan L,Zhang L,Zhang W,Wu X,Li Y,Yan B,Zhu X,Liu X,Yang C,Xu J,Zhou G,Xu A,Li H,Liu Ydoi
10.1093/hmg/ddt586subject
Has Abstractpub_date
2014-04-15 00:00:00pages
2210-9issue
8eissn
0964-6906issn
1460-2083pii
ddt586journal_volume
23pub_type
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