Cargando…
IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children
Genetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with clearance of hepatitis C virus. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Mali...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042471/ https://www.ncbi.nlm.nih.gov/pubmed/33850301 http://dx.doi.org/10.1038/s41435-021-00127-7 |
_version_ | 1783678135751933952 |
---|---|
author | Prokunina-Olsson, Ludmila Morrison, Robert D. Obajemu, Adeola Mahamar, Almahamoudou Kim, Sungduk Attaher, Oumar Florez-Vargas, Oscar Sidibe, Youssoufa Onabajo, Olusegun O. Hutchinson, Amy A. Manning, Michelle Kwan, Jennifer Brand, Nathan Dicko, Alassane Fried, Michal Albert, Paul S. Mbulaiteye, Sam M. Duffy, Patrick E. |
author_facet | Prokunina-Olsson, Ludmila Morrison, Robert D. Obajemu, Adeola Mahamar, Almahamoudou Kim, Sungduk Attaher, Oumar Florez-Vargas, Oscar Sidibe, Youssoufa Onabajo, Olusegun O. Hutchinson, Amy A. Manning, Michelle Kwan, Jennifer Brand, Nathan Dicko, Alassane Fried, Michal Albert, Paul S. Mbulaiteye, Sam M. Duffy, Patrick E. |
author_sort | Prokunina-Olsson, Ludmila |
collection | PubMed |
description | Genetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with clearance of hepatitis C virus. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we genotyped functional variants IFNL4-rs368234815, IFNL4-rs117648444, and IFNL3-rs4803217 and analyzed episodes of malaria, gastrointestinal, and respiratory infections recorded at 30,626 clinic visits from birth up to 5 years of age. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), rs368234815-dG allele was most strongly associated with an earlier time-to-first episode of gastrointestinal infections (p = 0.003). The risk of experiencing an infection episode during the follow-up was also significantly increased with rs368234815-dG allele, with OR = 1.53, 95%CI (1.13–2.07), p = 0.005 for gastrointestinal infections and OR = 1.30, 95%CI (1.02–1.65), p = 0.033 for malaria. All the associations for the moderately linked rs4803217 (r(2) = 0.78 in this set) were weaker and lost significance after adjusting for rs368234815. We also analyzed all outcomes in relation to IFN-λ4-P70S groups. Our results implicate IFN-λ4 and not IFN-λ3 as the primary functional cause of genetic associations with increased overall risk and younger age at first clinical episodes but not with recurrence or intensity of several common pediatric infections. |
format | Online Article Text |
id | pubmed-8042471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80424712021-04-13 IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children Prokunina-Olsson, Ludmila Morrison, Robert D. Obajemu, Adeola Mahamar, Almahamoudou Kim, Sungduk Attaher, Oumar Florez-Vargas, Oscar Sidibe, Youssoufa Onabajo, Olusegun O. Hutchinson, Amy A. Manning, Michelle Kwan, Jennifer Brand, Nathan Dicko, Alassane Fried, Michal Albert, Paul S. Mbulaiteye, Sam M. Duffy, Patrick E. Genes Immun Article Genetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with clearance of hepatitis C virus. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we genotyped functional variants IFNL4-rs368234815, IFNL4-rs117648444, and IFNL3-rs4803217 and analyzed episodes of malaria, gastrointestinal, and respiratory infections recorded at 30,626 clinic visits from birth up to 5 years of age. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), rs368234815-dG allele was most strongly associated with an earlier time-to-first episode of gastrointestinal infections (p = 0.003). The risk of experiencing an infection episode during the follow-up was also significantly increased with rs368234815-dG allele, with OR = 1.53, 95%CI (1.13–2.07), p = 0.005 for gastrointestinal infections and OR = 1.30, 95%CI (1.02–1.65), p = 0.033 for malaria. All the associations for the moderately linked rs4803217 (r(2) = 0.78 in this set) were weaker and lost significance after adjusting for rs368234815. We also analyzed all outcomes in relation to IFN-λ4-P70S groups. Our results implicate IFN-λ4 and not IFN-λ3 as the primary functional cause of genetic associations with increased overall risk and younger age at first clinical episodes but not with recurrence or intensity of several common pediatric infections. Nature Publishing Group UK 2021-04-13 2021 /pmc/articles/PMC8042471/ /pubmed/33850301 http://dx.doi.org/10.1038/s41435-021-00127-7 Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Prokunina-Olsson, Ludmila Morrison, Robert D. Obajemu, Adeola Mahamar, Almahamoudou Kim, Sungduk Attaher, Oumar Florez-Vargas, Oscar Sidibe, Youssoufa Onabajo, Olusegun O. Hutchinson, Amy A. Manning, Michelle Kwan, Jennifer Brand, Nathan Dicko, Alassane Fried, Michal Albert, Paul S. Mbulaiteye, Sam M. Duffy, Patrick E. IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children |
title | IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children |
title_full | IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children |
title_fullStr | IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children |
title_full_unstemmed | IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children |
title_short | IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children |
title_sort | ifn-λ4 is associated with increased risk and earlier occurrence of several common infections in african children |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042471/ https://www.ncbi.nlm.nih.gov/pubmed/33850301 http://dx.doi.org/10.1038/s41435-021-00127-7 |
work_keys_str_mv | AT prokuninaolssonludmila ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT morrisonrobertd ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT obajemuadeola ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT mahamaralmahamoudou ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT kimsungduk ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT attaheroumar ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT florezvargasoscar ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT sidibeyoussoufa ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT onabajooluseguno ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT hutchinsonamya ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT manningmichelle ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT kwanjennifer ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT brandnathan ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT dickoalassane ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT friedmichal ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT albertpauls ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT mbulaiteyesamm ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren AT duffypatricke ifnl4isassociatedwithincreasedriskandearlieroccurrenceofseveralcommoninfectionsinafricanchildren |