Candidate polymorphisms and severe malaria in a Malian population

Abstract

Malaria is a major health burden in sub-Saharan African countries, including Mali. The disease is complex, with multiple genetic determinants influencing the observed variation in response to infection, progression, and severity. We assess the influence of sixty-four candidate loci, including the sickle cell polymorphism (HbS), on severe malaria in a case-control study consisting of over 900 individuals from Bamako, Mali. We confirm the known protective effects of the blood group O and the HbS AS genotype on life-threatening malaria. In addition, our analysis revealed a marginal susceptibility effect for the CD40 ligand (CD40L)+220C allele. The lack of statistical evidence for other candidates may demonstrate the need for large-scale genome-wide association studies in malaria to discover new polymorphisms. It also demonstrates the need for establishing the region-specific repertoire of functional variation in important genes, including the glucose-6-phosphatase deficiency gene, before embarking on focused genotyping.

Figure 1. Minimum p-values from tests of association for the autosomal SNPs ^*.

^*Genotypic tests of dominant, recessive, general, heterozygous advantage, and additive models, adjusted for HbS and ethnicity; in this analysis controls include uncomplicated malaria cases; the dashed line represents a p-value of 0.002.