Premium
The genetic risk of acute seizures in A frican children with falciparum malaria
Author(s) -
Kariuki Symon M.,
Rockett Kirk,
Clark Taane G.,
Reyburn Hugh,
Agbenyega Tsiri,
Taylor Terrie E.,
Birbeck Gretchen L.,
Williams Thomas N.,
Newton Charles R. J. C.
Publication year - 2013
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12173
Subject(s) - malaria , plasmodium falciparum , medicine , cerebral malaria , epilepsy , immunology , biology , psychiatry
Summary Purpose 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. Methods Logistic regression was used to investigate genetic associations with malaria‐associated seizures ( MAS ) and complex MAS (repetitive, prolonged, or focal seizures) in four M alaria GEN A frican sites, namely: B lantyre, M alawi; K ilifi, K enya; K umasi, G hana; and M uheza, T anzania. The analysis was repeated for five inheritance models (dominant, heterozygous, recessive, additive, and general) and adjusted for potential confounders and multiple testing. Key Findings 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 K ilifi (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 K umasi (p = 0.00033), but none in the pooled analysis. Focal MAS were strongly associated with IL ‐20 receptor A ‐rs1555498 in M uheza (p = 0.00016), but none in the pooled analysis. Prolonged MAS were strongly associated with complement receptor 1‐rs17047660 in K ilifi (p = 0.00121) and glucose‐6‐phosphate dehydrogenase‐rs1050828 in females in the pooled analysis (p = 0.00155). Repetitive MAS were strongly associated with EMR 1‐rs373533 in K umasi (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 EMR 1‐rs373533 in K umasi (p = 0.00019) and IL 10‐rs3024500 in the pooled analysis across the sites (p = 0.00064). Significance 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 A frica. These associations differed according to phenotype of seizures and site.