Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso
Abstract Background Genetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of t...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-021-03628-y |
| _version_ | 1818922911217483776 |
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| author | Hamatandi Magloire Natama Eduard Rovira-Vallbona Meryam Krit Pieter Guetens Hermann Sorgho M. Athanase Somé Maminata Traoré-Coulibaly Innocent Valéa Petra F. Mens Henk D. F. H. Schallig Dirk Berkvens Luc Kestens Halidou Tinto Anna Rosanas-Urgell |
| author_facet | Hamatandi Magloire Natama Eduard Rovira-Vallbona Meryam Krit Pieter Guetens Hermann Sorgho M. Athanase Somé Maminata Traoré-Coulibaly Innocent Valéa Petra F. Mens Henk D. F. H. Schallig Dirk Berkvens Luc Kestens Halidou Tinto Anna Rosanas-Urgell |
| author_sort | Hamatandi Magloire Natama |
| collection | DOAJ |
| description | Abstract Background Genetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of their adaptive immune system, the protective effect of maternal antibodies and fetal haemoglobin. This study investigated the association between genetic variation in innate immune response genes and malaria susceptibility during the first year of life in 656 infants from a birth cohort survey performed in Nanoro, Burkina Faso. Methods Seventeen single nucleotide polymorphisms (SNPs) in 11 genes of the immune system previously associated with different malaria phenotypes were genotyped using TaqMan allelic hybridization assays in a Fluidigm platform. Plasmodium falciparum infection and clinical disease were documented by active and passive case detection. Case–control association analyses for both alleles and genotypes were carried out using univariate and multivariate logistic regression. For cytokines showing significant SNP associations in multivariate analyses, cord blood supernatant concentrations were measured by quantitative suspension array technology (Luminex). Results Genetic variants in IL-1β (rs1143634) and FcγRIIA/CD32 (rs1801274)—both in allelic, dominant and co-dominant models—were significantly associated with protection from both P. falciparum infection and clinical malaria. Furthermore, heterozygote individuals with rs1801274 SNP in FcγRIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P = 0.024), a cytokine whose production is promoted by the binding of IgG immune complexes to Fcγ receptors on effector immune cells. Conclusions These findings indicate that genetic polymorphisms in genes driving innate immune responses are associated to malaria susceptibility during the first year of life, possibly by modulating production of inflammatory mediators. |
| first_indexed | 2024-12-20T02:01:03Z |
| format | Article |
| id | doaj.art-28641e0d45224781aa5692bfdde868b9 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-20T02:01:03Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-28641e0d45224781aa5692bfdde868b92022-12-21T19:57:19ZengBMCMalaria Journal1475-28752021-02-0120111410.1186/s12936-021-03628-yGenetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina FasoHamatandi Magloire Natama0Eduard Rovira-Vallbona1Meryam Krit2Pieter Guetens3Hermann Sorgho4M. Athanase Somé5Maminata Traoré-Coulibaly6Innocent Valéa7Petra F. Mens8Henk D. F. H. Schallig9Dirk Berkvens10Luc Kestens11Halidou Tinto12Anna Rosanas-Urgell13Department of Biomedical Sciences, Institute of Tropical MedicineDepartment of Biomedical Sciences, Institute of Tropical MedicineDepartment of Biomedical Sciences, Institute of Tropical MedicineDepartment of Biomedical Sciences, Institute of Tropical MedicineUnité de Recherche Clinique de Nanoro, Institut de Recherche en Sciences de La SantéUnité de Recherche Clinique de Nanoro, Institut de Recherche en Sciences de La SantéUnité de Recherche Clinique de Nanoro, Institut de Recherche en Sciences de La SantéUnité de Recherche Clinique de Nanoro, Institut de Recherche en Sciences de La SantéDepartment of Medical Microbiology-Parasitology Unit, Academic Medical Centre, Amsterdam University Medical CentresDepartment of Medical Microbiology-Parasitology Unit, Academic Medical Centre, Amsterdam University Medical CentresDepartment of Biomedical Sciences, Institute of Tropical MedicineDepartment of Biomedical Sciences, Institute of Tropical MedicineUnité de Recherche Clinique de Nanoro, Institut de Recherche en Sciences de La SantéDepartment of Biomedical Sciences, Institute of Tropical MedicineAbstract Background Genetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of their adaptive immune system, the protective effect of maternal antibodies and fetal haemoglobin. This study investigated the association between genetic variation in innate immune response genes and malaria susceptibility during the first year of life in 656 infants from a birth cohort survey performed in Nanoro, Burkina Faso. Methods Seventeen single nucleotide polymorphisms (SNPs) in 11 genes of the immune system previously associated with different malaria phenotypes were genotyped using TaqMan allelic hybridization assays in a Fluidigm platform. Plasmodium falciparum infection and clinical disease were documented by active and passive case detection. Case–control association analyses for both alleles and genotypes were carried out using univariate and multivariate logistic regression. For cytokines showing significant SNP associations in multivariate analyses, cord blood supernatant concentrations were measured by quantitative suspension array technology (Luminex). Results Genetic variants in IL-1β (rs1143634) and FcγRIIA/CD32 (rs1801274)—both in allelic, dominant and co-dominant models—were significantly associated with protection from both P. falciparum infection and clinical malaria. Furthermore, heterozygote individuals with rs1801274 SNP in FcγRIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P = 0.024), a cytokine whose production is promoted by the binding of IgG immune complexes to Fcγ receptors on effector immune cells. Conclusions These findings indicate that genetic polymorphisms in genes driving innate immune responses are associated to malaria susceptibility during the first year of life, possibly by modulating production of inflammatory mediators.https://doi.org/10.1186/s12936-021-03628-yMalariaPlasmodium falciparumImmunogenetic variantsCytokinesInnate immunity |
| spellingShingle | Hamatandi Magloire Natama Eduard Rovira-Vallbona Meryam Krit Pieter Guetens Hermann Sorgho M. Athanase Somé Maminata Traoré-Coulibaly Innocent Valéa Petra F. Mens Henk D. F. H. Schallig Dirk Berkvens Luc Kestens Halidou Tinto Anna Rosanas-Urgell Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso Malaria Journal Malaria Plasmodium falciparum Immunogenetic variants Cytokines Innate immunity |
| title | Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso |
| title_full | Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso |
| title_fullStr | Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso |
| title_full_unstemmed | Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso |
| title_short | Genetic variation in the immune system and malaria susceptibility in infants: a nested case–control study in Nanoro, Burkina Faso |
| title_sort | genetic variation in the immune system and malaria susceptibility in infants a nested case control study in nanoro burkina faso |
| topic | Malaria Plasmodium falciparum Immunogenetic variants Cytokines Innate immunity |
| url | https://doi.org/10.1186/s12936-021-03628-y |
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