Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda.
<h4>Background</h4>Individuals genetically susceptible to high schistosomiasis worm burden may contribute disproportionately to transmission and could be prioritized for control. Identifying genes involved may guide development of therapy.<h4>Methodology/principal findings</h4&g...
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Public Library of Science (PLoS)
2023-11-01
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| Series: | PLoS Neglected Tropical Diseases |
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| author | Oscar Asanya Nyangiri Julius Mulindwa Joyce Namulondo Anna Kitibwa Jacent Nassuuna Alison Elliott Magambo Phillip Kimuda Alex Boobo Barbara Nerima Moses Adriko Nathan J Dunton Gaganjit Kaur Madhan Mark Kristiansen Miriam Casacuberta-Partal Harry Noyes Enock Matovu TrypanoGEN+ Research group of the H3Africa consortium |
| author_facet | Oscar Asanya Nyangiri Julius Mulindwa Joyce Namulondo Anna Kitibwa Jacent Nassuuna Alison Elliott Magambo Phillip Kimuda Alex Boobo Barbara Nerima Moses Adriko Nathan J Dunton Gaganjit Kaur Madhan Mark Kristiansen Miriam Casacuberta-Partal Harry Noyes Enock Matovu TrypanoGEN+ Research group of the H3Africa consortium |
| author_sort | Oscar Asanya Nyangiri |
| collection | DOAJ |
| description | <h4>Background</h4>Individuals genetically susceptible to high schistosomiasis worm burden may contribute disproportionately to transmission and could be prioritized for control. Identifying genes involved may guide development of therapy.<h4>Methodology/principal findings</h4>A cohort of 606 children aged 10-15 years were recruited in the Albert Nile region of Uganda and assessed for Schistosoma mansoni worm burden using the Up-Converting Particle Lateral Flow (UCP-LF) test detecting circulating anodic antigen (CAA), point-of-care Circulating Cathodic Antigen (POC-CCA) and Kato-Katz tests. Whole genome genotyping was conducted on 326 children comprising the top and bottom 25% of worm burden. Linear models were fitted to identify variants associated with worm burden in preselected candidate genes. Expression quantitative trait locus (eQTL) analysis was conducted for candidate genes with UCP-LF worm burden included as a covariate. Single Nucleotide Polymorphism loci associated with UCP-LF CAA included IL6 rs2066992 (OR = 0.43, p = 0.0006) and rs7793163 (OR = 2.0, p = 0.0007); IL21 SNP kgp513476 (OR 1.79, p = 0.0025) and IL17B SNP kgp708159 (OR = 0.35, p = 0.0028). A haplotype in the IL10 locus was associated with lower worm burden (OR = 0.53, p = 0.015) and overlapped SNPs rs1800896, rs1800871 and rs1800872. Significant haplotypes (p<0.05, overlapping significant SNP) associated with worm burden were observed in IL6 and the Th17 pathway IL12B and IL17B genes. There were significant eQTL in the IL6, IL5, IL21, IL25 and IFNG regions.<h4>Conclusions</h4>Variants associated with S. mansoni worm burden were in IL6, FCN2, RNASE3, IL10, IL12B and IL17B gene loci. However only eQTL associations remained significant after Bonferroni correction. In summary, immune balance, pathogen recognition and Th17 pathways may play a role in modulating Schistosoma worm burden. Individuals carrying risk variants may be targeted first in allocation of control efforts to reduce the burden of schistosomiasis in the community. |
| format | Article |
| id | doaj-art-2ab6d4fb87d4440c8b600bae9a0b301a |
| institution | OA Journals |
| issn | 1935-2727 1935-2735 |
| language | English |
| publishDate | 2023-11-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Neglected Tropical Diseases |
| spelling | doaj-art-2ab6d4fb87d4440c8b600bae9a0b301a2025-08-20T02:33:44ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352023-11-011711e001179610.1371/journal.pntd.0011796Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda.Oscar Asanya NyangiriJulius MulindwaJoyce NamulondoAnna KitibwaJacent NassuunaAlison ElliottMagambo Phillip KimudaAlex BooboBarbara NerimaMoses AdrikoNathan J DuntonGaganjit Kaur MadhanMark KristiansenMiriam Casacuberta-PartalHarry NoyesEnock MatovuTrypanoGEN+ Research group of the H3Africa consortium<h4>Background</h4>Individuals genetically susceptible to high schistosomiasis worm burden may contribute disproportionately to transmission and could be prioritized for control. Identifying genes involved may guide development of therapy.<h4>Methodology/principal findings</h4>A cohort of 606 children aged 10-15 years were recruited in the Albert Nile region of Uganda and assessed for Schistosoma mansoni worm burden using the Up-Converting Particle Lateral Flow (UCP-LF) test detecting circulating anodic antigen (CAA), point-of-care Circulating Cathodic Antigen (POC-CCA) and Kato-Katz tests. Whole genome genotyping was conducted on 326 children comprising the top and bottom 25% of worm burden. Linear models were fitted to identify variants associated with worm burden in preselected candidate genes. Expression quantitative trait locus (eQTL) analysis was conducted for candidate genes with UCP-LF worm burden included as a covariate. Single Nucleotide Polymorphism loci associated with UCP-LF CAA included IL6 rs2066992 (OR = 0.43, p = 0.0006) and rs7793163 (OR = 2.0, p = 0.0007); IL21 SNP kgp513476 (OR 1.79, p = 0.0025) and IL17B SNP kgp708159 (OR = 0.35, p = 0.0028). A haplotype in the IL10 locus was associated with lower worm burden (OR = 0.53, p = 0.015) and overlapped SNPs rs1800896, rs1800871 and rs1800872. Significant haplotypes (p<0.05, overlapping significant SNP) associated with worm burden were observed in IL6 and the Th17 pathway IL12B and IL17B genes. There were significant eQTL in the IL6, IL5, IL21, IL25 and IFNG regions.<h4>Conclusions</h4>Variants associated with S. mansoni worm burden were in IL6, FCN2, RNASE3, IL10, IL12B and IL17B gene loci. However only eQTL associations remained significant after Bonferroni correction. In summary, immune balance, pathogen recognition and Th17 pathways may play a role in modulating Schistosoma worm burden. Individuals carrying risk variants may be targeted first in allocation of control efforts to reduce the burden of schistosomiasis in the community.https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011796&type=printable |
| spellingShingle | Oscar Asanya Nyangiri Julius Mulindwa Joyce Namulondo Anna Kitibwa Jacent Nassuuna Alison Elliott Magambo Phillip Kimuda Alex Boobo Barbara Nerima Moses Adriko Nathan J Dunton Gaganjit Kaur Madhan Mark Kristiansen Miriam Casacuberta-Partal Harry Noyes Enock Matovu TrypanoGEN+ Research group of the H3Africa consortium Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda. PLoS Neglected Tropical Diseases |
| title | Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda. |
| title_full | Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda. |
| title_fullStr | Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda. |
| title_full_unstemmed | Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda. |
| title_short | Variants of IL6, IL10, FCN2, RNASE3, IL12B and IL17B loci are associated with Schistosoma mansoni worm burden in the Albert Nile region of Uganda. |
| title_sort | variants of il6 il10 fcn2 rnase3 il12b and il17b loci are associated with schistosoma mansoni worm burden in the albert nile region of uganda |
| url | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011796&type=printable |
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