Haptoglobin HP2-2 genotype, alpha-thalassaemia and acute seizures in children living in a malaria-endemic area
Idro R., Williams TN., Gwer S., Uyoga S., Macharia A., Opi H., Atkinson S., Maitland K., Kager PA., Kwiatkowski D., Neville BG., Newton CR.
Polymorphisms of the haptoglobin (HP) gene and deletions in alpha-globin gene (alpha-thalassaemia) are common in malaria-endemic Africa. The same region also has high incidence rates for childhood acute seizures. The haptoglobin HP2-2 genotype has been associated with idiopathic generalized epilepsies and altered iron metabolism in children with alpha-thalassaemia can potentially interfere with neurotransmission and increase the risk of seizures. We investigated the hypothesis that the HP2-2 genotype and the common African alpha-globin gene deletions are associated with the increased risk of seizures. 288 children aged 3-156 months admitted with acute seizures to Kilifi District Hospital (Kenya), were matched for ethnicity to an equal number of community controls. The proportion of cases (72/288 [25.0%]) and controls (80/288 [27.8%]) with HP2-2 genotype was similar, p=0.499. The allele frequency of HP2 gene in cases (49.3%) and controls (48.6%) was also similar, p=0.814. Similarly, we found no significant difference between the proportion of cases (177/267 [66.3%]) and controls (186/267 [69.7%]) with deletions in alpha-globin gene (p=0.403). Among cases, HP2-2 polymorphism and deletions in alpha-globin gene were neither associated with changes in the type, number or duration of seizures nor did they affect outcome. We conclude that the HP2-2 polymorphism and deletions in alpha-globin gene are not risk factors for acute seizures in children. Future studies should examine other susceptibility genes.