Department of Internal Medicine and Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, 6525 HP, the Netherlands.
Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Odense, DK-5000, Denmark; Center for Clinical Research and Prevention, Frederiksberg and Bispebjerg Hospital, DK-2000, Frederiksberg, Denmark.
J Genet Genomics. 2023 Jun;50(6):434-446. doi: 10.1016/j.jgg.2023.01.002. Epub 2023 Jan 18.
Genetic variation is a key factor influencing cytokine production capacity, but which genetic loci regulate cytokine production before and after vaccination, particularly in African population is unknown. Here, we aimed to identify single-nucleotide polymorphisms (SNPs) controlling cytokine responses after microbial stimulation in infants of West-African ancestry, comprising of low-birth-weight neonates randomized to bacillus Calmette-Guérin (BCG) vaccine-at-birth or to the usual delayed BCG. Genome-wide cytokine cytokine quantitative trait loci (cQTL) mapping revealed 12 independent loci, of which the LINC01082-LINC00917 locus influenced more than half of the cytokine-stimulation pairs assessed. Furthermore, nine distinct cQTLs were found among infants randomized to BCG. Functional validation confirmed that several complement genes affect cytokine response after BCG vaccination. We observed a limited overlap of common cQTLs between the West-African infants and cohorts of Western European individuals. These data reveal strong population-specific genetic effects on cytokine production and may indicate new opportunities for therapeutic intervention and vaccine development in African populations.
遗传变异是影响细胞因子产生能力的关键因素，但哪些遗传位点调节接种前后的细胞因子产生，特别是在非洲人群中尚不清楚。在这里，我们旨在确定西非裔婴儿在微生物刺激后控制细胞因子反应的单核苷酸多态性（SNP），这些婴儿包括随机分配到卡介苗（BCG）出生时疫苗或常规延迟 BCG 的低出生体重新生儿。全基因组细胞因子数量性状基因座（cQTL）图谱显示了 12 个独立的基因座，其中 LINC01082-LINC00917 基因座影响了评估的一半以上细胞因子刺激对。此外，在随机分配到 BCG 的婴儿中发现了 9 个不同的 cQTL。功能验证证实，几种补体基因会影响 BCG 接种后的细胞因子反应。我们观察到西非婴儿和西欧个体队列之间常见 cQTL 的重叠有限。这些数据显示细胞因子产生具有强烈的人群特异性遗传效应，可能为非洲人群的治疗干预和疫苗开发提供新的机会。
