@article{fdi:010061197,
  title = {{E}pistatic interactions between apolipoprotein {E} and hemoglobin {S} genes in regulation of malaria parasitemia},
  author = {{R}ougeron, {V}. and {W}oods, {C}. {M}. and {T}iedje, {K}. {E}. and {B}odeau-{L}ivinec, {F}. and {M}igot {N}abias, {F}lorence and {D}eloron, {P}hilippe and {L}uty, {A}drian and {F}owkes, {F}. {J}. {I}. and {D}ay, {K}. {P}.},
  editor = {},
  language = {{ENG}},
  abstract = {{A}polipoprotein {E} is a monomeric protein secreted by the liver and responsible for the transport of plasma cholesterol and triglycerides. {T}he {APOE} gene encodes 3 isoforms epsilon 4, epsilon 3 and epsilon 2 with {APOE} epsilon 4 associated with higher plasma cholesterol levels and increased pathogenesis in several infectious diseases ({HIV}, {HSV}). {G}iven that cholesterol is an important nutrient for malaria parasites, we examined whether {APOE} epsilon 4 was a risk factor for {P}lasmodium infection, in terms of prevalence or parasite density. {A} cross sectional survey was performed in 508 children aged 1 to 12 years in {G}abon during the wet season. {C}hildren were screened for {P}lasmodium spp. infection, {APOE} and hemoglobin {S} ({H}b{S}) polymorphisms. {M}edian parasite densities were significantly higher in {APOE} epsilon 4 children for {P}lasmodium spp. densities compared to non-{APOE} epsilon 4 children. {W}hen stratified for {H}b{S} polymorphisms, median {P}lasmodium spp. densities were significantly higher in {H}b{AA} children if they had an {APOE} epsilon 4 allele compared to those without an {APOE} epsilon 4 allele. {W}hen considering non-{APOE} epsilon 4 children, there was no quantitative reduction of {P}lasmodium spp. parasite densities for {H}b{AS} compared to {H}b{AA} phenotypes. {N}o influence of {APOE} epsilon 4 on successful {P}lasmodium liver cell invasion was detected by multiplicity of infection. {T}hese results show that the {APOE} epsilon 4 allele is associated with higher median malaria parasite densities in children likely due to the importance of cholesterol availability to parasite growth and replication. {R}esults suggest an epistatic interaction between {APOE} and {H}b{S} genes such that sickle cell trait only had an effect on parasite density in {APOE} epsilon 4 children. {T}his suggests a linked pathway of regulation of parasite density involving expression of these genes. {T}hese findings have significance for understanding host determinants of regulation of malaria parasite density, the design of clinical trials as well as studies of co-infection with {P}lasmodium and other pathogens.},
  keywords = {},
  booktitle = {},
  journal = {{P}los {O}ne},
  volume = {8},
  numero = {10},
  pages = {e76924},
  ISSN = {1932-6203},
  year = {2013},
  DOI = {10.1371/journal.pone.0076924},
  URL = {https://www.documentation.ird.fr/hor/fdi:010061197},
}