Variants in the Toll‐interacting protein gene (rs5743899) and susceptibility to Plasmodium falciparum malaria infection in West Africa

Abstract

Malaria remains a very significant disease, with high rates of morbidity and mortality, contributing to economic inequities in endemic countries. The parasite is widely distributed with extensive genetic polymorphisms, increasing rates of drug resistance and lack of an effective vaccine. Dysregulated immune response, especially focused on signaling or pathogen recognition factors in immune system pathway is critical to understanding disease severity or pathophysiology. Toll‐interacting protein (TOLLIP) regulates human toll‐like receptor signaling pathways, and its polymorphisms have been associated with infectious disease. To elucidate whether TOLLIP polymorphisms are associated with Plasmodium falciparum infections in West Africa, we examined the genetic frequency of TOLLIP gene polymorphisms (rs5743899 and rs3750920) in 110 patients, with symptomatic, clinical malaria (diagnosis confirmed by microscopy and polymrease chain reaction) and 371 controls (PCR‐negative), recruited from south‐west Nigeria. Genomic DNA samples between groups were analyzed with a polymerase chain reaction and restriction fragment length polymorphism assay. Our results show that the Tollip rs5743899 mutant variant had the lowest frequency compared to the wild type variant, in addition to an extensive disparity between malaria‐infected patients and uninfected controls. There was a significant difference in the genotypic frequency of the rs5743899 mutant variant between malaria‐infected and control groups respectively in West Africa (13.7% versus 20.8%; p=0.09), but not in the rs3750920 polymorphism (57.3% versus 49.3%; p=0.16). This present observation reveals that Tollip gene rs5743899 mutant variant is potentially associated with Plasmodium falciparum malaria infection in West Africa. Interestingly, the most common haplotype among both groups is H2 (40.4% versus 44.1% for malaria‐infected and uninfected controls respectively), combining the mutant variant for both Tollip polymorphisms. Conclusively, this report shows that susceptibility to malaria infection in West Africa and potential contribution to disease severity or preponderance is significantly associated with host genetic variation, with toll‐interacting protein gene a significant member.Support or Funding InformationFunding provided by College of Health Sciences and Technology Faculty Development and Laboratory Support Fund, Rochester Institute of Technology