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. 2018 Dec 13;17(1):467.
doi: 10.1186/s12936-018-2618-5.

Mitochondrial Gene Sequence Variants in Children With Severe Malaria Anaemia With or Without Lactic Acidosis: A Case Control Study

Free PMC article

Mitochondrial Gene Sequence Variants in Children With Severe Malaria Anaemia With or Without Lactic Acidosis: A Case Control Study

Casey Fowler et al. Malar J. .
Free PMC article


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.

Keywords: Anemia; DNA sequence; Lactic acidosis; Malaria; Mitochondria; Tissue oxygenation.


Fig. 1
Fig. 1
Distribution of mitochondrial gene nucleotide variants in oxidative phosphorylation genes. The number of variants per person relative to the revised Cambridge Reference Sequence over the region of mitochondria encoding genes for oxidative phosphorylation is shown. Data from patients with high blood lactate levels (n = 36) and normal blood lactate levels (n = 37) are shown. Variants found at locations outside the coding sequence for the oxidative phosphorylation proteins are not included. Left panel shows results for any form of sequence variant. Right panel shows non-synonymous variants only. Horizontal bars are medians and inter-quartile ranges
Fig. 2
Fig. 2
Non-synonymous variants in oxidative phosphorylation genes among patients with and without elevated blood lactate levels. Patients with high blood lactate (n = 36) are on the left of the solid black line; patients with normal lactate levels (n = 37) are on the right. Each patient is represented by a column and each variant location by a row. Non-synonymous variants are shown as red squares. To simplify the figure, nucleotide positions (rows) without variants are not shown

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    1. Gething PW, Casey DC, Weiss DJ, Bisanzio D, Bhatt S, Cameron E, et al. Mapping Plasmodium falciparum mortality in Africa between 1990 and 2015. N Engl J Med. 2016;375:2435–2445. doi: 10.1056/NEJMoa1606701. - DOI - PMC - PubMed
    1. Mangano VD, Modiano D. An evolutionary perspective of how infection drives human genome diversity: the case of malaria. Curr Opin Immunol. 2014;30:39–47. doi: 10.1016/j.coi.2014.06.004. - DOI - PubMed
    1. Cserti-Gazdewich C, Dhabangi A, Musoke C, Ssewanyana I, Ddungu H, Nakiboneka- Ssenabulya D, et al. Cytoadherence in paediatric malaria: ABO blood group, CD36, and ICAM-1 expression and severe Plasmodium falciparum infection. Br J Haematol. 2012;159:223–236. doi: 10.1111/bjh.12014. - DOI - PMC - PubMed
    1. Kwiatkowski D. How malaria has affected the human genome and what human genetics can teach us about malaria. Am J Hum Genet. 2005;77:171–190. doi: 10.1086/432519. - DOI - PMC - PubMed
    1. Dhabangi A, Ainomugisha B, Cserti-Gazdewich C, Ndungu H, Kyeyune D, Musisi E, et al. Effect of transfusion of red blood cells with longer vs shorter storage duration on elevated blood lactate levels in children with severe anemia: the TOTAL randomized trial. JAMA. 2015;314:2514–2523. doi: 10.1001/jama.2015.13977. - DOI - PubMed