Full-Length Original Research
The genetic risk of acute seizures in African children with falciparum malaria
Article first published online: 24 APR 2013
Wiley Periodicals, Inc. © 2013 International League Against Epilepsy
Volume 54, Issue 6, pages 990–1001, June 2013
How to Cite
Kariuki, S. M., Rockett, K., Clark, T. G., Reyburn, H., Agbenyega, T., Taylor, T. E., Birbeck, G. L., Williams, T. N. and Newton, C. R. J. C. (2013), The genetic risk of acute seizures in African children with falciparum malaria. Epilepsia, 54: 990–1001. doi: 10.1111/epi.12173
- Issue published online: 4 JUN 2013
- Article first published online: 24 APR 2013
- Manuscript Accepted: 6 MAR 2013
- Wellcome Trust. Grant Number: 083744
- Research Training Fellowship. Grant Number: 099782/Z/12/Z
- European Union EVIMalR Network 7 Programme. Grant Number: WT077383/Z/05/Z
- Bill and Melinda Gates Foundation
- Medical Research Council. Grant Number: G0600230
- Seizure phenotypes;
- Malaria-associated seizures;
- Genetic risk
It is unclear why some children with falciparum malaria develop acute seizures and what determines the phenotype of seizures. We sought to determine if polymorphisms of malaria candidate genes are associated with acute seizures.
Logistic regression was used to investigate genetic associations with malaria-associated seizures (MAS) and complex MAS (repetitive, prolonged, or focal seizures) in four MalariaGEN African sites, namely: Blantyre, Malawi; Kilifi, Kenya; Kumasi, Ghana; and Muheza, Tanzania. The analysis was repeated for five inheritance models (dominant, heterozygous, recessive, additive, and general) and adjusted for potential confounders and multiple testing.
Complex phenotypes of seizures constituted 71% of all admissions with MAS across the sites. MAS were strongly associated with cluster of differentiation-ligand-rs3092945 in females in Kilifi (p = 0.00068) and interleukin (IL)-17 receptor E-rs708567 in the pooled analysis across the sites (p = 0.00709). Complex MAS were strongly associated with epidermal growth factor module-containing mucin-like hormone receptor (EMR)1-rs373533 in Kumasi (p = 0.00033), but none in the pooled analysis. Focal MAS were strongly associated with IL-20 receptor A-rs1555498 in Muheza (p = 0.00016), but none in the pooled analysis. Prolonged MAS were strongly associated with complement receptor 1-rs17047660 in Kilifi (p = 0.00121) and glucose-6-phosphate dehydrogenase-rs1050828 in females in the pooled analysis (p = 0.00155). Repetitive MAS were strongly associated with EMR1-rs373533 in Kumasi (p = 0.00003) and cystic fibrosis transmembrane conductance receptor-rs17140229 in the pooled analysis (p = 0.00543). MAS with coma/cerebral malaria were strongly associated with EMR1-rs373533 in Kumasi (p = 0.00019) and IL10-rs3024500 in the pooled analysis across the sites (p = 0.00064).
We have identified a number of genetic associations that may explain the risk of seizures in >2,000 cases admitted to hospitals with MAS across four sites in Africa. These associations differed according to phenotype of seizures and site.