Case-control approach to identify Plasmodium falciparum polymorphisms associated with severe malaria

Area of Science:

• Genetics
• Malariology
• Genomics

Background:

• Plasmodium falciparum genome studies require dense marker loci for identifying phenotypically-associated polymorphisms.
• Thailand's low malaria endemicity offers higher linkage disequilibrium (LD) for initial association studies.

Purpose of the Study:

• To assess linkage disequilibrium (LD) across the Plasmodium falciparum genome.
• To identify polymorphisms associated with severe malaria in Thailand.

Main Methods:

• Assessed LD using dispersed and chromosome 2-specific microsatellite loci in 100 P. falciparum isolates.
• Conducted a disease association study comparing severe malaria cases (113) and mild malaria controls (245).
• Genotyped polymorphisms in erythrocyte binding antigen (EBA) and reticulocyte binding homologue (Rh) genes.

Main Results:

• Dispersed microsatellite loci showed minimal LD, while loci on chromosome 2 (<5 kb apart) exhibited significant LD.
• Identified significant allelic associations between severe malaria and polymorphisms in eba175 (codons 388-90) and Rh1 (codon 667).

Conclusions:

• Dense genotypic markers are essential for Plasmodium falciparum allelic association studies, even in areas with moderate endemicity and higher LD.
• Polymorphisms in eba175 and Rh1 genes are linked to severe malaria and require further study.