IFN-λ4 genetic variants influence clinical malaria episodes in a cohort of Kenyan children

Malaria Journal

Sidney Ogolla¹  Arlene E. Dent²  Adeola Obajemu³  Ludmilla Prokunina-Olsson³  Gabriela Samayoa-Reyes⁴  Katherine Sabourin⁴  Rosemary Rochford⁴  Conner Jackson⁴ 

[1] Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya;Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA;Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA;University of Colorado Anschutz Medical Campus, Aurora, CO, USA;

关键词: Plasmodium falciparum;    Malaria;    Innate Immunity;    Type III Interferon;    IFN-λ4;   

DOI  :  10.1186/s12936-021-03689-z

来源: Springer

【 摘 要 】

BackgroundInterferon (IFN)- λ4, a type III IFN, production is controlled by a dinucleotide frameshift variant (rs368234815-dG/TT) within the first exon of the IFNL4 gene. Carriers of the IFNL4-dG allele but not the IFNL4-TT allele are able to produce the IFN-λ4 protein. Patients with hepatitis C virus that do not produce the IFN-λ4 protein have higher rates of viral clearance suggesting a potential inhibitory role of IFN-λ4 in liver-tropic infections.MethodsIn this study, it was investigated whether children infected with Plasmodium falciparum, which has a well-characterized liver stage infection, would be more susceptible to clinical malaria relative to their IFNL4-rs368234815 allele. A cohort of 122 children from a malaria holoendemic region of Kenya was analysed. Episodes of clinical malaria and upper respiratory tract infections (URTIs) were determined using information collected from birth to 2 years of age. The dinucleotide frameshift variant IFNL4-rs368234815-dG/TT was genotyped using a TaqMan assay.ResultsIn this cohort, 33% of the study participants had the dG/dG genotype, 45% had the dG/TT genotype, and 22% had TT/TT genotype. The number and time to first episode of clinical malaria and URTIs with respect to the IFNL4-rs368234815 allele was evaluated. It was found that children that carried the IFNL4-rs368234815-dG allele had an increased number of clinical malaria episodes. In addition, there was a significant association between earlier age of first malaria infection with carriers of the IFNL4-dG allele (p-value: 0.021).ConclusionThe results suggest that the ability to produce IFN-λ4 negatively affects host immune protection against P. falciparum malaria in Kenyan children.

【 授权许可】

CC BY