title: A genome-wide association study identifies polymorphisms in the HLA-DR region associated with non-response to hepatitis B vaccination in Chinese Han populations.
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.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and.
authors.forename: Liping
authors.initials: L
authors.lastname: Pan
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Wu
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Li
authors.forename: Bingyu
authors.initials: B
authors.lastname: Yan
authors.forename: Xilin
authors.initials: X
authors.lastname: Zhu
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Gangqiao
authors.initials: G
authors.lastname: Zhou
authors.forename: Aiqiang
authors.initials: A
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006509:Hepatitis B / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy*; D017325:Hepatitis B Vaccines / Q000627:therapeutic use*; D006515:Hepatitis B virus / Q000502:physiology; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D014611:Vaccination
chemical_list: D006684:HLA-DR Antigens; D017325:Hepatitis B Vaccines