@article{fdi:010066047,
  title = {{M}odulation of malaria phenotypes by pyruvate kinase ({PKLR}) variants in a {T}hai population},
  author = {van {B}ruggen, {R}. and {G}ualtieri, {C}. and {I}liescu, {A}. and {C}heepsunthorn, {C}. {L}. and {M}ungkalasut, {P}. and {T}rape, {J}ean-{F}ran{\c{c}}ois and {M}odiano, {D}. and {S}irima, {B}. {S}. and {S}inghasivanon, {P}. and {L}athrop, {M}. and {S}akuntabhai, {A}. and {B}ureau, {J}. {F}. and {G}ros, {P}.},
  editor = {},
  language = {{ENG}},
  abstract = {{P}yruvate kinase ({PKLR}) is a critical erythrocyte enzyme that is required for glycolysis and production of {ATP}. {W}e have shown that {P}klr deficiency in mice reduces the severity (reduced parasitemia, increased survival) of blood stage malaria induced by infection with {P}lasmodium chabaudi {AS}. {L}ikewise, studies in human erythrocytes infected ex vivo with {P}. falciparum show that presence of host {PK}-deficiency alleles reduces infection phenotypes. {W}e have characterized the genetic diversity of the {PKLR} gene, including haplotype structure and presence of rare coding variants in two populations from malaria endemic areas of {T}hailand and {S}enegal. {W}e investigated the effect of {PKLR} genotypes on rich longitudinal datasets including haematological and malaria-associated phenotypes. {A} coding and possibly damaging variant ({R}41{Q}) was identified in the {T}hai population with a minor allele frequency of similar to 4.7%. {A}rginine 41 ({R}41) is highly conserved in the pyruvate kinase family and its substitution to {G}lutamine ({R}41{Q}) affects protein stability. {H}eterozygosity for {R}41{Q} is shown to be associated with a significant reduction in the number of attacks with {P}lasmodium falciparum, while correlating with an increased number of {P}lasmodium vivax infections. {T}hese results strongly suggest that {PKLR} protein variants may affect the frequency, and the intensity of malaria episodes induced by different {P}lasmodium parasites in humans living in areas of endemic malaria.},
  keywords = {{THAILANDE}},
  booktitle = {},
  journal = {{P}los {O}ne},
  volume = {10},
  numero = {12},
  pages = {e0144555 [18 p.]},
  ISSN = {1932-6203},
  year = {2015},
  DOI = {10.1371/journal.pone.0144555},
  URL = {https://www.documentation.ird.fr/hor/fdi:010066047},
}