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

• Published in: Malaria journal Vol. 20; no. 1; p. 196
• Main Authors: Samayoa-Reyes, Gabriela, Jackson, Conner, Ogolla, Sidney, Sabourin, Katherine, Obajemu, Adeola, Dent, Arlene E, Prokunina-Olsson, Ludmilla, Rochford, Rosemary
• Format: Journal Article
• Language: English
• Published: England BioMed Central 21.04.2021; BMC
• Subjects: Alleles; Birth weight; Children; Cohorts; Dehydrogenases; Enzymes; Genetic diversity; Genetic variance; Genotype & phenotype; Genotypes; Hepatitis; Hepatitis C; Human diseases; IFN-λ4; Immune clearance; Infections; Innate Immunity; Interferon; Laboratories; Liver; Malaria; Plasmodium falciparum; Polymorphism; Population; Pregnancy; Proteins; Questionnaires; Respiratory tract; Respiratory tract diseases; Type III Interferon; Vector-borne diseases; Viruses; Kenya; Africa; Plasmodium falciparum; Malaria; IFN-λ4; Innate Immunity; Type III Interferon
• ISSN: 1475-2875; 1475-2875
• DOI: 10.1186/s12936-021-03689-z

Interferon (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. In 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. In 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). The results suggest that the ability to produce IFN-λ4 negatively affects host immune protection against P. falciparum malaria in Kenyan children.