Abstract
BACKGROUND: Evolutionary pressure by Plasmodium falciparum malaria is known to have favoured a large number of human gene adaptations, but there is surprisingly little investigation of the effect of malaria on human mitochondrial sequence variation. Plasmodium falciparum infection can cause severe malaria anaemia (SMA) with insufficient tissue oxygenation, lactic acidosis and death. Despite equal degrees of severe anaemia, some individuals develop lactic acidosis while others do not. A case-control study design was used to investigate whether differences in host mitochondrial gene sequences were associated with lactic acidosis in SMA. Full mitochondrial sequences were obtained from 36 subjects with SMA complicated by lactic acidosis and 37 subjects with SMA without lactic acidosis. The two groups were matched for age, sex, and degree of anaemia. RESULTS: Compared with the reference sequence, a median of 60 nucleotide variants per individual (interquartile range 4-91) was found, with an average frequency of 3.97 variants per 1000 nucleotides. The frequency and distribution of non-synonymous DNA variants in genes associated with oxidative phosphorylation were not statistically different between the two groups. Non-synonymous variants predicted to have the most disruptive effect on proteins responsible for oxidative phosphorylation were present at a similar frequency in both groups. CONCLUSIONS: Lactic acidosis in SMA does not appear to be consistently associated with the high prevalence of any mitochondrial gene variant.