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Genetic regulators of cytokine responses upon BCG vaccination in children from West Africa.

Journal of genetics and genomics = Yi chuan xue bao

Authors: Collins K Boahen, S J C F M Moorlag, Kristoffer Jarlov Jensen, Vasiliki Matzaraki, Stephanie Fanucchi, Ivan Monteiro, Charlotte de Bree, Ezio T Fok, Musa Mhlanga, Leo A B Joosten, Peter Aaby, Christine Stabell Benn, Mihai G Netea, Vinod Kumar

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 (cQTLs) after microbial stimulation in infants of West-African ancestry, comprising of low-birth-weight neonates randomized to bacillus Calmette-Guérin (BCG) vaccine-at-birth (intervention) or to the usual delayed BCG (control). Genome-wide cytokine QTL mapping revealed 12 independent cQTLs 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.

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

PMID: 36681271

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