The Association between Toll-Like Receptor 4 (-8984c/G) and 299 Asp/Gly and Severe Malaria Disease in Children below 3 Years in Siaya County Western Kenya
| dc.contributor.author | Omwandho, John Robert Charles | |
| dc.date.accessioned | 2024-09-26T06:48:52Z | |
| dc.date.available | 2024-09-26T06:48:52Z | |
| dc.date.issued | 2024-05 | |
| dc.description | A Thesis Submitted in Partial Fulfillment of the Requirements for the Award of Degree of Master of Science (Biotechnology) in the School of Pure and Applied Science of Kenyatta University, May 2024 | |
| dc.description.abstract | The high paediatric mortality and morbidity linked to Malaria in Africa is majorly caused by the parasite: Plasmodium falciparum with many complications characterized by severe anaemia and parasitemia. Severe Malaria Anaemia (SMA; Hb<5.0g/L accompanied by parasitemia of any density) manifests in young children below three years old. Nonetheless, the absence of understanding regarding the molecular underpinnings of SMA continues to hinder progress in creating successful treatments. Genetic susceptibility factors provide a means to decipher the intricate molecular processes at play. Toll like Receptor signalling pathways play an essential immunological role in helping to clear the parasites. However, the contributions of genetic variations to SMA pathogenesis are partially understood. Therefore, the study aimed to unravel the associations between Toll-Like Receptor 4 (-8984C/G) and 299 Asp/Gly polymorphisms and vulnerability to SMA and parasitemia. Samples from children (n= 426) diagnosed with malaria at Siaya County Referral Hospital were analysed. DNA extraction and genotyping were performed on dry blood spots using Gentra Systems Isolation Kit and TaqMan® 5' allelic discrimination Assay-By-Design high-throughput technique respectively. The association between Toll-like receptor-4 (-8984C/G) and 299 Asp/Gly polymorphism and SMA was determined using bivariate logistic regression analysis while controlling for anaemia confounders; Bacteraemia (co-infections) and HIV-1, alpha-thalassemia (traits) and sickle cell. The association between parasitemia and carriage of respective genotypes and haplotypes was done using Kruskal Wallis test/ Mann U Whitney where applicable. Bivariate regression analysis revealed that the TLR-4 (-8984 C/G) genotypes (GG vs. GC, OR = 0.53, 95% CI = 0.07-3.91, P= 0.533, and GG vs. CC, OR = 1.02, 95% CI = 0.12–8.82, P= 0.988) and TLR-4 +299 Asp/Gly genotypes (Asp/Asp vs. Gly/Asp, OR = 1.66, 95% CI = 0.42–6.50, P=0.471) were not associated with SMA. Further, haplotypes of TLR-4 -8984G and +299Gly (OR; 2.70, CI; 0.70-10.48, P= 0.151), TLR-4 -8984G and +299Asp (OR; 0.72, CI; 0.15-3.51, P= 0.682) and TLR-4 -8984C and +299Asp (OR; 1.29 CI; 0.56-3.63, P = 0.636) were also not associated with SMA. Moreover, there was no association between genotypes of TLR-4 (8489G /C) [GG (18530), GC (18303) and CC (14952) P= 0.858] or TLR-4 (Asp + 299 Gly) [Asp/Asp (18770), Asp/Gly (37714) and Gly/Gly(67324) P= 0.482] with parasitemia. Similarly, the haplotypes of TLR-4 (G-8984C) + TLR-4 (Asp+299Gly), [G/Asp (P=0.887), C/Asp (P=0.884) and C/Gly (P= 0.4032)] had no association with parasitemia. The results demonstrated that TLR-4 (8489G/C) and TLR-4 (Asp+299 Gly) genotypes and haplotypes are not associated with SMA or parasitemia in the population of interest. The investigation outcomes are important in providing insights on the effect of polymorphism in immune cells in designing novel treatments and vaccinations in the fight against malaria. The study recommends further longitudinal studies to fully understand the functions of the polymorphisms in SMA. | |
| dc.description.sponsorship | Kenyatta University | |
| dc.identifier.uri | https://ir-library.ku.ac.ke/handle/123456789/28878 | |
| dc.language.iso | en | |
| dc.publisher | Kenyatta University | |
| dc.title | The Association between Toll-Like Receptor 4 (-8984c/G) and 299 Asp/Gly and Severe Malaria Disease in Children below 3 Years in Siaya County Western Kenya | |
| dc.type | Thesis |