Common apolipoprotein E polymorphisms and risk of clinical malaria in the Gambia

Apolipoprotein E (apoE) is a protein involved in the transport and metabolism of plasma cholesterol and triglycerides. The apolipoprotein E gene (APOE), located at chromosome 19q13.2, has three major alleles called e2, e3, and e4, defined by two single nucleotide polymorphisms (SNP) located in exon 4 at positions 3937 (T/C) and 4075 (C/T). The corresponding apoE isoforms differ at amino acid positions 112 (Cys for apoE2 and apoE3, Arg for apoE4) and 158 (Arg for apoE3 and apoE4, Cys for apoE2), and have been shown to have different functional and biochemical properties.1–4 APOE polymorphisms have been studied in relation to several genetic diseases and disorders. The APOE e4 allele has been associated with an increased risk of Alzheimer’s disease, coronary heart disease, and death after myocardial infarction.5–7 Conversely, the APOE e2 allele was found to have a protective effect on the occurrence of Alzheimer’s disease. However, in other studies, APOE e2 was associated with an increased risk of cardiovascular diseases and with some blood lipid abnormalities.8,9 It has been reported recently that APOE e2 homozygote children from Ghana became infected with Plasmodium falciparum at an earlier age than those carrying other APOE genotypes.10 In this study, performed in the Gambia, the APOE e2, e3, and e4 allele distributions were analysed in children with mild (338 cases) or severe (530 cases) malaria, and in individually matched control children (560 subjects). Additionally, the APOE Th1/E47 polymorphism located in the APOE promoter region11 was studied in a subset of children consisting of 183 severe malaria cases and 179 controls. ### Study subjects Between August 1989 and September 1990, 1428 children aged from 1 to 10 years were enrolled at the Royal Victoria Hospital of Banjul and at the Medical Research Council Hospital of Fajara, in the Gambia. Malaria …