IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children
In: Genes & Immunity, Jg. 22 (2021-05-01), Heft 1
academicJournal
- 44 - 55
Zugriff:
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 (r2 = 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.
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IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children
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Autor/in / Beteiligte Person: | 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 |
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Zeitschrift: | Genes & Immunity, Jg. 22 (2021-05-01), Heft 1 |
Veröffentlichung: | eScholarship, University of California, 2021 |
Medientyp: | academicJournal |
Umfang: | 44 - 55 |
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