1. IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children
- 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, and Duffy, Patrick E
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,Clinical Research ,Prevention ,Pediatric ,Genetics ,Digestive Diseases ,Infection ,Good Health and Well Being ,Alleles ,Child ,Genotype ,Hepacivirus ,Hepatitis C ,Humans ,Interferons ,Interleukins ,Polymorphism ,Single Nucleotide ,Immunology - Abstract
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.
- Published
- 2021