The genetic risk of acute seizures in African children with falciparum malaria.
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 a...
| Principais autores: | , , , , , , , , |
|---|---|
| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
2013
|
| _version_ | 1826264650872782848 |
|---|---|
| author | Kariuki, S Rockett, K Clark, T Reyburn, H Agbenyega, T Taylor, T Birbeck, G Williams, T Newton, C |
| author_facet | Kariuki, S Rockett, K Clark, T Reyburn, H Agbenyega, T Taylor, T Birbeck, G Williams, T Newton, C |
| author_sort | Kariuki, S |
| collection | OXFORD |
| description | 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 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. 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 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). 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 Africa. These associations differed according to phenotype of seizures and site. |
| first_indexed | 2024-03-06T20:11:15Z |
| format | Journal article |
| id | oxford-uuid:2aa1a83e-74d0-47f4-9f18-f15faa3d5b44 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:11:15Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:2aa1a83e-74d0-47f4-9f18-f15faa3d5b442022-03-26T12:26:10ZThe genetic risk of acute seizures in African children with falciparum malaria.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2aa1a83e-74d0-47f4-9f18-f15faa3d5b44EnglishSymplectic Elements at Oxford2013Kariuki, SRockett, KClark, TReyburn, HAgbenyega, TTaylor, TBirbeck, GWilliams, TNewton, CPURPOSE: 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 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. 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 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). 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 Africa. These associations differed according to phenotype of seizures and site. |
| spellingShingle | Kariuki, S Rockett, K Clark, T Reyburn, H Agbenyega, T Taylor, T Birbeck, G Williams, T Newton, C The genetic risk of acute seizures in African children with falciparum malaria. |
| title | The genetic risk of acute seizures in African children with falciparum malaria. |
| title_full | The genetic risk of acute seizures in African children with falciparum malaria. |
| title_fullStr | The genetic risk of acute seizures in African children with falciparum malaria. |
| title_full_unstemmed | The genetic risk of acute seizures in African children with falciparum malaria. |
| title_short | The genetic risk of acute seizures in African children with falciparum malaria. |
| title_sort | genetic risk of acute seizures in african children with falciparum malaria |
| work_keys_str_mv | AT kariukis thegeneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT rockettk thegeneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT clarkt thegeneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT reyburnh thegeneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT agbenyegat thegeneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT taylort thegeneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT birbeckg thegeneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT williamst thegeneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT newtonc thegeneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT kariukis geneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT rockettk geneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT clarkt geneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT reyburnh geneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT agbenyegat geneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT taylort geneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT birbeckg geneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT williamst geneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria AT newtonc geneticriskofacuteseizuresinafricanchildrenwithfalciparummalaria |