PDF(Pubmed)
Abstract：
BACKGROUND: This study aimed to explore how genetic variations in individuals impact neutralization activity post-mRNA vaccination, recognizing the critical role vaccination plays in curbing COVID-19 spread and the necessity of ensuring vaccine efficacy amidst genetic diversity.
METHODS: In a 4-week clinical pilot study, 534 healthy subjects received their first COVID vaccine dose, followed by the second dose. Antibody levels were evaluated thrice. From this pool, 120 participants were selected and divided into high- and low-antibody groups based on their levels. Genomic DNA was isolated from peripheral blood mononuclear cells for pilot genome-wide association studies (GWAS) conducted on a single platform. Real-time PCR was used to confirm differences in gene expression identified via GWAS analysis.
RESULTS: Three SNPs exceeded the level of p < 1.0 × 10-3. The rs7795433 SNP of the HDAC9 gene (7q21.1) showed the strongest association with COVID-19 vaccination under the additive model (OR = 5.63; p = 3 × 10-5). In the PCR experiments, the AA genotype group showed that the gene expression level of HDAC9 was likely to be decreased in the low-antibody-formation group at the time of vaccination.
CONCLUSIONS: We found that AA genotype holders (rs7795433 SNP of the HDAC9 gene) have a high probability of having a higher antibody count when vaccinated, and GG type holders have a high probability of the opposite. These findings show that the genetic characteristics of vaccinated people may affect antibody production after COVID vaccination.
METHODS: In a 4-week clinical pilot study, 534 healthy subjects received their first COVID vaccine dose, followed by the second dose. Antibody levels were evaluated thrice. From this pool, 120 participants were selected and divided into high- and low-antibody groups based on their levels. Genomic DNA was isolated from peripheral blood mononuclear cells for pilot genome-wide association studies (GWAS) conducted on a single platform. Real-time PCR was used to confirm differences in gene expression identified via GWAS analysis.
RESULTS: Three SNPs exceeded the level of p < 1.0 × 10-3. The rs7795433 SNP of the HDAC9 gene (7q21.1) showed the strongest association with COVID-19 vaccination under the additive model (OR = 5.63; p = 3 × 10-5). In the PCR experiments, the AA genotype group showed that the gene expression level of HDAC9 was likely to be decreased in the low-antibody-formation group at the time of vaccination.
CONCLUSIONS: We found that AA genotype holders (rs7795433 SNP of the HDAC9 gene) have a high probability of having a higher antibody count when vaccinated, and GG type holders have a high probability of the opposite. These findings show that the genetic characteristics of vaccinated people may affect antibody production after COVID vaccination.
摘要：
背景：本研究旨在探讨个体的遗传变异如何影响mRNA疫苗接种后的中和活性，认识到疫苗接种在遏制COVID-19传播方面的关键作用，以及在遗传多样性中确保疫苗效力的必要性。
方法：在为期4周的临床试点研究中，534名健康受试者接受了他们的第一剂COVID疫苗，其次是第二次剂量。对抗体水平进行三次评价。从这个游泳池里，选择了120名参与者，并根据其水平分为高抗体组和低抗体组。从外周血单核细胞中分离基因组DNA,用于在单一平台上进行的先导全基因组关联研究(GWAS)。使用实时PCR来确认通过GWAS分析鉴定的基因表达的差异。
结果：三个SNP超过p<1.0×10-3的水平。在加性模型下，HDAC9基因(7q21.1)的rs7795433SNP与COVID-19疫苗接种的相关性最强(OR=5.63；p=3×10-5)。在PCR实验中,AA基因型组显示,低抗体形成组的HDAC9基因表达水平在接种时可能降低.
结论：我们发现AA基因型持有者（HDAC9基因的rs7795433SNP）在接种疫苗时具有更高的抗体计数的可能性很高，与GG型持有者相反的概率很高。这些发现表明，接种疫苗的人的遗传特征可能会影响COVID疫苗接种后的抗体产生。
方法：在为期4周的临床试点研究中，534名健康受试者接受了他们的第一剂COVID疫苗，其次是第二次剂量。对抗体水平进行三次评价。从这个游泳池里，选择了120名参与者，并根据其水平分为高抗体组和低抗体组。从外周血单核细胞中分离基因组DNA,用于在单一平台上进行的先导全基因组关联研究(GWAS)。使用实时PCR来确认通过GWAS分析鉴定的基因表达的差异。
结果：三个SNP超过p<1.0×10-3的水平。在加性模型下，HDAC9基因(7q21.1)的rs7795433SNP与COVID-19疫苗接种的相关性最强(OR=5.63；p=3×10-5)。在PCR实验中,AA基因型组显示,低抗体形成组的HDAC9基因表达水平在接种时可能降低.
结论：我们发现AA基因型持有者（HDAC9基因的rs7795433SNP）在接种疫苗时具有更高的抗体计数的可能性很高，与GG型持有者相反的概率很高。这些发现表明，接种疫苗的人的遗传特征可能会影响COVID疫苗接种后的抗体产生。
