Extensive interethnic diversity of cytokine interleukin‐10 promoter gene (rs1800872) single nucleotide polymorphisms and association with malaria infection
Authors: Aziz Najihah , Adedokun Samuel , Snyder Tara J , Farid Iman , Ojurongbe Olusola , Thomas Bolaji 
Published: November 2023

A major hallmark of infectious diseases is inflammation, particularly significant in endemic countries, where low levels of antigenic stimulation that is insufficient to cause disease are significant contributors to chronic inflammation, disrupting immunological balance. Interleukin (IL)‐10 is a cytokine produced by many cell types, stimulating the differentiation of innate and adaptive immunity cells and the control of inflammatory processes. We hypothesize that the diversity in inflammatory response is most importantly dependent on host genetic pathways, with this inter‐individual diversity more pronounced in individuals from Africa, thereby possessing cytokine gene variants abnormally affecting immune response. To this end, we examined the interethnic frequency of cytokine IL‐10 (rs1800872) promoter gene polymorphisms in three, disparate, well‐characterized population groups as well as malaria‐infected group and determined its association with disease. Genomic DNA samples were obtained from 189, 189 and 159 Africans, African Americans and Caucasians respectively. In addition, 105 Plasmodium falciparum malaria‐infected patients from south‐west Nigeria were included, with comparative analysis among and between groups carried out with a polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) assay. There was a statistically significant (p=1.07E‐03) interethnic diversity in the genotypic frequency of IL‐10 (rs1800872) mutant variant between population groups (20.1% versus 14.8% versus 6.3% for Africans, African Americans and Caucasians respectively). A similar interethnic observation was made for allelic frequency of IL‐10 polymorphism (p=4.35E‐08). This significant interethnic diversity clarifies the heterogeneous distribution of this polymorphism between groups and its essentiality in differential regulation of disease susceptibility or outcome. Interestingly, we found no significant difference in either genotypic (27.6% versus 20.1%; p=0.14) or allelic frequency (46.7% versus 43.9%; p=0.5) of IL‐10 (rs1800872) mutant variant between malaria‐infected patients and controls from West Africa. The lack of a significant difference in the malaria‐infected group is not surprising since malaria infection will drive T cell differentiation into Th1 cells, rather than Th2 cells, for which IL‐10 cytokine anti‐inflammatory properties would inhibit protective response. The possibility that the reported elevated levels of serum IL‐10 in malaria infection and consequent disease severity is regulated by host polymorphic variants deserves further investigation. This confirms our hypothesis that elucidating interethnic host genetic variations before initiating population‐stratified association studies are imperative. In addition, this host genetic variations are potential contributors to individual or sub‐continental differences in disease susceptibility and prevalence.Support or Funding InformationFunding provided by College of Health Sciences and Technology Faculty Development and Laboratory Support Fund, Rochester Institute of Technology