Table1_Genetic variants in BAT2 are associated with immune responsiveness to influenza vaccination.pdf

Background: Influenza is a global public health problem for its detrimental impact on human health. Annual vaccination is the most effective prevention of influenza infection. Identifying host genetic factors associated with the responsiveness to influenza vaccines can provide clues for developing more effective influenza vaccines. In this study, we aimed to explore whether the single nucleotide polymorphisms in BAT2 are associated with the antibody responses to influenza vaccines.
Method: A nested case-control study was conducted in this research. 1968 healthy volunteers were enrolled and 1,582 of them from a Chinese Han population were eligible for further research. According to the hemagglutination inhibition titers of subjects against all influenza vaccine strains, a total of 227 low responders and 365 responders were included in the analysis. Six tag single nucleotide polymorphisms in the coding region of BAT2 were selected and genotyped using the MassARRAY technology platform. Univariable and multivariable analyses were conducted to evaluate the relationship between variants and antibody responses to influenza vaccination.
Results: Multivariable logistic regression analysis showed that, compared with the BAT2 rs1046089GG genotype, the GA + AA genotype was correlated with decreased risk of low responsiveness to influenza vaccines after adjusting for gender and age (p = 1.12E-03, OR = .562, 95%CI: .398–.795). rs9366785 GA + AA genotype was associated with a higher risk of low responsiveness to influenza vaccination compared with the GG genotype (p = .003, OR = 1.854, 95%CI: 1.229–2.799). The haplotype consisting of BAT2 rs2280801-rs10885-rs1046089-rs2736158-rs1046080-rs9366785 CCAGAG was correlated with a higher level of antibody response to influenza vaccines compared with haplotype CCGGAG (p < .001, OR = .37, 95%CI: .23–.58).
Conclusion: Genetic variants in BAT2 were statistically associated with the immune response to influenza vaccination among the Chinese population. Identifying these variants will provide clues for further research on novel broad-spectrum influenza vaccines, and improve the individualized influenza vaccination scheme.

研究背景：流感对人类健康具有有害影响，是全球性公共卫生问题。每年接种流感疫苗是预防流感感染最有效的手段。明确与流感疫苗应答相关的宿主遗传因素，可为开发更高效的流感疫苗提供线索。本研究旨在探讨BAT2基因中的单核苷酸多态性（single nucleotide polymorphisms）是否与流感疫苗的抗体应答存在关联。
研究方法：本研究采用巢式病例对照研究设计。共纳入1968名健康志愿者，其中来自中国汉族人群的1582名符合后续研究纳入标准。根据受试者针对所有流感疫苗毒株的血凝抑制滴度，最终纳入227名低应答者与365名应答者进行分析。选取BAT2基因编码区的6个标签单核苷酸多态性，采用MassARRAY技术平台进行基因分型。通过单变量与多变量分析，评估基因变异与流感疫苗抗体应答之间的关联。
研究结果：多变量logistic回归分析显示，在校正性别与年龄因素后，相较于BAT2 rs1046089 GG基因型，GA+AA基因型与流感疫苗低应答风险降低显著相关（p=1.12×10^-3，OR=0.562，95%CI：0.398~0.795）。相较于GG基因型，rs9366785 GA+AA基因型与流感疫苗低应答风险升高显著相关（p=0.003，OR=1.854，95%CI：1.229~2.799）。由BAT2 rs2280801-rs10885-rs1046089-rs2736158-rs1046080-rs9366785组成的单倍型CCAGAG，相较于单倍型CCGGAG，与流感疫苗抗体应答水平升高显著相关（p<0.001，OR=0.37，95%CI：0.23~0.58）。
研究结论：在中国人群中，BAT2基因的遗传变异与流感疫苗接种后的免疫应答存在统计学关联。明确此类遗传变异可为新型广谱流感疫苗的后续研究提供线索，并有助于优化个体化流感疫苗接种方案。