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dc.contributor.authorArama, Charles
dc.contributor.authorDiarra, Issa
dc.contributor.authorKouriba, Bourèma
dc.date.accessioned2018-03-20T13:14:12Z
dc.date.available2018-03-20T13:14:12Z
dc.date.issued2018-02-15
dc.identifier.citationArama C, Diarra I, Kouriba B, et al. (2018). Malaria severity: Possible influence of the E670G PCSK9 polymorphism: A preliminary case-control study in Malian children. PLoS ONE, 13(2), Ee0192850, DOI: https://doi.org/10.1371/journal.pone.0192850en_US
dc.identifier.urihttp://hdl.handle.net/10713/7584
dc.descriptionAdditional authors: Sirois, Francine; Fedoryak, Olesya; Thera, Mahamadou A.; Coulibaly, Drissa; Lyke, Kirsten E.; Plowe, Christopher V.; Chrétien, Michel; Doumbo, Ogobara K.; Mbikay, Majambuen_US
dc.description.abstractAim: Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is a hepatic secretory protein which promotes the degradation of low-density lipoprotein receptors leading to reduced hepatic uptake of plasma cholesterol. Non-synonymous single-nucleotide polymorphisms in its gene have been linked to hypo- or hyper- cholesterolemia, depending on whether they decrease or increase PCSK9 activity, respectively. Since the proliferation and the infectivity of Plasmodium spp. partially depend on cholesterol from the host, we hypothesize that these PCSK9 genetic polymorphisms could influence the course of malaria infection in individuals who carry them. Here we examined the frequency distribution of one dominant (C679X) and two recessive (A443T, I474V) hypocholesterolemic polymorphisms as well as that of one recessive hypercholesterolemic polymorphism (E670G) among healthy and malaria-infected Malian children. Methods: Dried blood spots were collected in Bandiagara, Mali, from 752 age, residence and ethnicity- matched children: 253 healthy controls, 246 uncomplicated malaria patients and 253 severe malaria patients. Their genomic DNA was extracted and genotyped for the above PCSK9 polymorphisms using Taqman assays. Associations of genotype distributions and allele frequencies with malaria were evaluated. Results: The minor allele frequency of the A443T, I474V, E670G, and C679X polymorphisms in the study population sample was 0.12, 0.20, 0.26, and 0.02, respectively. For each polymorphism, the genotype distribution among the three health conditions was statistically insignificant, but for the hypercholesterolemic E670G polymorphism, a trend towards association of the minor allele with malaria severity was observed (P = 0.035). The association proved to be stronger when allele frequencies between healthy controls and severe malaria cases were compared (Odd Ratio: 1.34; 95% Confidence Intervals: 1.04±1.83); P = 0.031). Conclusions: Carriers of the minor allele of the E670G PCSK9 polymorphism might be more susceptible to severe malaria. Further investigation of the cholesterol regulating function of PCSK9 in the pathophysiology of malaria is needed.en_US
dc.description.sponsorshipThis work was funded by grants from the Institut MeÂrieux (www.institut-merieux.com) as well as the Richard and Edith Strauss Foundation to MC. The Bandiagara case/control study was supported by a contract N01AI85346 and a cooperative agreement U19AI065683 from the National Institute of Allergy and Infectious Diseases and grant D43TW001589 to OKD from the Fogarty International Center, National Institutes of Health,USA.en_US
dc.language.isoen_USen_US
dc.publisherSan Francisco: PLOSen_US
dc.rightsOpen Accessen_US
dc.subjectPCSK9en_US
dc.subject.meshMalariaen_US
dc.subject.meshPlasmodium--pathogenicityen_US
dc.subject.meshPolymorphism, Single Nucleotideen_US
dc.subject.meshProprotein Convertase 9--geneticsen_US
dc.subject.meshVirulenceen_US
dc.subject.meshMalien_US
dc.subject.meshAdolescenten_US
dc.subject.meshChilden_US
dc.subject.meshChild, Preschoolen_US
dc.subject.meshInfanten_US
dc.titleMalaria severity: Possible influence of the E670G PCSK9 polymorphism: A preliminary case-control study in Malian childrenen_US
dc.typeArticleen_US
dc.description.urinameFull Texten_US
refterms.dateFOA2019-02-19T18:12:39Z


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