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

Journal of Genetics and Genomics 2023年第6期50卷 434-446页

作者： 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 department of Internal Medicine and Radboud Institute of Molecular Life Sciences(RIMLS) Radboud University Medical CenterNjmegen6525 HPthe Netherlands department of Internal Medicine and Radboud Center for Infectious Diseases(RCI) Radboud University Medical CenterNjmegen6525 HPthe Netherlands Odense Patient Data Explorative Network University of Southern Denmark/Odense University HospitalOdenseDK-5000Denmark Center for Clinical Research and Prevention Frederiksberg and Bispebjerg HospitalDK-2000FrederiksbergDenmark Lemba Therapeutics Nijmegen6525 GAthe Netherlands Bandim Health Project Indepth NetworkBissaucodex 1004Guinea-Bissau Epigenomics&Single Cell Biophysics Group Department of Cell Biology FNWIRadboud Institute for Molecular Life Sciences(RIMLS)Njmegen6525 HPtheNetherlands department of Human Genetics Radboud University Medical Center6525 HPthe Netherlands Bandim Health Project Statens Serum InstitutCopenhagen SDK-2300Denmark Danish Institute for Advanced Study University of Southern DenmarkOdenseDK-5000Denmark department of Internal Medicine and Radboud Center for Infectious Diseases Radboud University Medical CenterNijmegen6525 HPthe Netherlands department for Immunology and Metabolism Life and Medical Sciences Institute(LIMES)University of BonnGermany University of Groningen University Medical Center GroningenDepartment of GeneticsGroningen970o0 RBthe Netherlands Nitte(deemed to be University) Nitte University Centre for Science Education and Research(NUCSER)Medical Sciences ComplexDeralakatteMangalore575018India

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 ***,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-Gue rin(BCG)vaccine-at-birth or to the usual delayed ***-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 ***,nine distinct cQTLs were found among infants randomized to *** validation confirmed that several complement genes affect cytokine response after BCG *** observed a limited overlap of common cQTLs between the West-African infants and cohorts of Western European *** data reveal strong population-specific genetic effects on cytokine production and may indicate new opportunities for therapeutic intervention and vaccine development in African populations.

关键词： Cytokines Geneticvariation West Africa Immunogenomics QTL BCG

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