Wider Clinical Impacts of Malaria-Protective Human Genetic Variants at KEMRI Wellcome Trust Research Programme (KWTRP)

Wider Clinical Impacts of Malaria-Protective Human Genetic Variants

• Several human genetic traits have been shown to strongly protect against malaria, such as sickle cell trait (HbAS), the rare Dantu blood group variant, alpha thalassaemia, blood group O, and G6PD deficiency. However, the wider clinical consequences of these variants and their impacts on immune response are not well characterised.
• We aim to analyse the wider health impacts of these malaria-protective variants by investigating the association between these variants and ward admission events in ~20,000 ward admission cases. We will extract DNA and genotype of these SNPs in the 20,000 samples and use logistic regression analyses to investigate the relationship between these variants and other clinical diseases. This will enable a better understanding of the wider clinical impacts of genetic variants that are strongly protective against malaria.
• We will also investigate the impact of these variants on immune response by isolating monocytes from peripheral blood mononuclear cells (PBMCs) collected from individuals across genotype groups, and stimulate them with laboratory parasite strains to investigate the variation in inflammatory response evoked. We will use flow cytometry to measure the activation and adhesion markers on monocytes, and pro-inflammatory cytokines produced in the culture supernatant.