IFN-λ4 is associated with increased risk and earlier occurrence of several common infections in African children.

Autor: Prokunina-Olsson L; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA. prokuninal@mail.nih.gov., Morrison RD; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA., Obajemu A; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA., Mahamar A; Malaria Research & Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Sciences Techniques and Technologies of Bamako, Bamako, Mali., Kim S; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, 20850, USA., Attaher O; Malaria Research & Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Sciences Techniques and Technologies of Bamako, Bamako, Mali., Florez-Vargas O; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA., Sidibe Y; Malaria Research & Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Sciences Techniques and Technologies of Bamako, Bamako, Mali., Onabajo OO; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA., Hutchinson AA; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA., Manning M; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA., Kwan J; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20892, USA., Brand N; Department of Surgery, University of California San Francisco, San Francisco, CA, 94143, USA., Dicko A; Malaria Research & Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Sciences Techniques and Technologies of Bamako, Bamako, Mali., Fried M; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA., Albert PS; Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, 20850, USA., Mbulaiteye SM; Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892-9776, USA., Duffy PE; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Jazyk: angličtina
Zdroj: Genes and immunity [Genes Immun] 2021 May; Vol. 22 (1), pp. 44-55. Date of Electronic Publication: 2021 Apr 13.
DOI: 10.1038/s41435-021-00127-7
Abstrakt: 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.
Databáze: MEDLINE
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