Abstract
BackgroundEvolutionary 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.ResultsCompared 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.ConclusionsLactic acidosis in SMA does not appear to be consistently associated with the high prevalence of any mitochondrial gene variant.
Highlights
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
Fowler et al Malar J (2018) 17:467 it has been shown that lactic acidosis can result from severe anaemia with inadequate tissue oxygenation, and that lactic acidosis is relieved by transfusion of red blood cells with restoration of tissue oxygenation [5], there is no recognized explanation for the observation that some children develop lactic acidosis with severe malaria anaemia (SMA) while others do not
Because oxygen-dependent bioenergetics occurs within mitochondria and relies in part on proteins encoded by mitochondrial genes, this study was designed to explore whether genetic differences in host mitochondria might account for differences in tolerance to the decreased tissue oxygenation that accompanies SMA
Summary
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. A case–control study design was used to investigate whether differences in host mitochon‐ drial gene sequences were associated with lactic acidosis in SMA. Fowler et al Malar J (2018) 17:467 it has been shown that lactic acidosis can result from severe anaemia with inadequate tissue oxygenation, and that lactic acidosis is relieved by transfusion of red blood cells with restoration of tissue oxygenation [5], there is no recognized explanation for the observation that some children develop lactic acidosis with SMA while others do not. To investigate whether or not mitochondrial sequence variation might be associated with the development of lactic acidosis in severe anaemia, a matched case–control study among children with SMA was performed to compare the entire mitochondrial genome among severely anemic children with and without lactic acidosis
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