Common apolipoprotein E polymorphisms and risk of clinical malaria in the Gambia.(Letter to JMG)

J Med Genet 2004;41:21-24

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 [epsilon]2, [epsilon]3, and [epsilon]4, 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 [epsilon]4 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 [epsilon]2 allele was found to have a protective effect on the occurrence of Alzheimer's disease. However, in other studies, APOE [epsilon]2 was associated with an increased risk of cardiovascular diseases and with some blood lipid abnormalities. (8 9) It has been reported recently that APOE [epsilon]2 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 [epsilon]2, [epsilon]3, and [epsilon]4 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 region (11) was studied in a subset of children consisting of 183 severe malaria cases and 179 controls.

MATERIALS AND METHODS

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 was diagnosed if a patient with an appropriate clinical picture had parasitaemia >2500/[micro]l, and relevant laboratory investigations did not suggest other diagnoses. Cerebral malaria was defined by a Blantyre coma score of more than 3 (persisting for more than 30 minutes after effective treatment of hypoglycaemia or convulsions) or repeated prolonged seizure (for more than 30 minutes) in a child with P falciparum parasitaemia and no other apparent cause of fits or coma. Severe malaria anaemia was defined as a haemoglobin level of less than 50 g/l on admission in a child with parasitaemia. Children with mild malaria had an uncomplicated febrile illness with P. falciparum parasitaemia and no other apparent cause of fever.

The group of severe malaria patients was matched to two control groups of children for age and area of residence. The mild controls were recruited at both hospitals and health centres in the study area. These children had mild, mostly infective, illnesses that did not require hospital admission and they did not have malarial parasites in their blood on microscopy. Severely infected controls were inpatients at the two hospitals, with a large range of other acute, mainly infective, illnesses but without evidence of current or recent malaria infection.

The ethnic composition of the population in this area is mixed: Mandinka (42%), Jola (14%), Wolof (14%), Fula (12%), and several less common ethnic groups. The children from the different groups were not matched for ethnic group; instead, analyses stratified with this variable were carried out. Details of this case control study have been described previously. (12)

The study had the approval of the Gambian Government and of the MRC Joint Ethical Committee, and consent was obtained from the parent …