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Human genetic variation influences Plasmodium falciparum drug resistance selection

Here we address the issue of the possible interplay between host genetic variation and the risk of acquiring Plasmodium falciparum drug-resistant strains. The involvement of human genetic variation as a possible co-factor in the selection and spread of P. falciparum drug resistance is a new tool in the study of malaria and possibly of other infectious diseases. The driving hypothesis of this approach is that parasite drug resistance could be affected both by ethnicity and human variability in the genes encoding for enzymes that metabolise antimalarials (cytochrome P450 liver enzymes). Understanding if parasite drug sensitivity is influenced and possibly modulated by human diversity can contribute to a better knowledge and control of the spread of drug resistance. So far, few studies have addressed this strategic issue. To explore this hypothesis we carried out an association analysis on 506 human/P. falciparum DNA samples from adult asymptomatic subjects belonging to three sympatric ethnic groups of Burkina Faso, an area of hyperendemic malaria in West Africa. Here we report that the prevalence of chloroquine-resistant infections (pfcrt 76T and/or pfmdr1 86Y) differs among sympatric ethnic groups, being higher in Mossi and Rimaibé compared to Fulani (OR: 2.24; 1.27-3.92; P = 0.007). Moreover, the human CYP2C8*2 variant, known to determine a poor drug metaboliser phenotype, is associated with P. falciparum chloroquine-resistant infections (OR: 1.66; 1.13-2.43; P = 0.008). The results strongly suggest that human genetic variation affects the dynamics of selection of parasite drug-resistance. We strongly believe that these observations are of general interest and may have important implications in public health.

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Correspondence to Giacomo Maria Paganotti.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Keywords

  • Malaria
  • Drug Resistance
  • Plasmodium Falciparum
  • Human Genetic Variation
  • Parasite Drug Resistance

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