Author/Authors :
Fedoryak, Olesya Functional Endoproteolysis Laboratory - Clinical Research Institute of Montreal, Quebec, Canada , Arama, Charles Malaria Research and Training Center - Department of Epidemiology of Parasitic Diseases International Center of Excellence in Research, University of Sciences - Technique and Technology of Bamako, Mali , Diarra, Issa Malaria Research and Training Center - Department of Epidemiology of Parasitic Diseases International Center of Excellence in Research, University of Sciences - Technique and Technology of Bamako, Mali , Kouriba, Bourema Malaria Research and Training Center - Department of Epidemiology of Parasitic Diseases International Center of Excellence in Research, University of Sciences - Technique and Technology of Bamako, Mali , Chretien, Michel Functional Endoproteolysis Laboratory - Clinical Research Institute of Montreal, Quebec, Canada , Mbikay, Majambu Functional Endoproteolysis Laboratory - Clinical Research Institute of Montreal, Quebec, Canada
Abstract :
Recent evidence suggests that proprotein convertase subtilisin/kexin type 9 (PCSK9), a downmodulator of cellular uptake of blood cholesterol, also negatively impacts host immune response to microbial infection. In this study, we investigated whether carrying the loss-of-function (LOF) rs562556 (c.1420 A > G; p.I474 V) PCSK9 single nucleotide polymorphism (SNP) affected the outcome of severe malaria in children. Archival DNA of a cohort of 207 Malian children suffering from severe malaria was genotyped for the rs562556 SNP. Sixty-four children were either heterozygous or homozygous for the minor G allele (carriers); 143 children were homozygous for the common A allele (noncarriers). Among carriers, there was one mortality case (1.6%), compared to 15 cases (10.5%) among noncarriers (p=0.0251), suggesting that the G allele is associated with better survival in severe malaria. Intriguingly, this allele did not negatively segregate with any of the clinical symptoms linked to mortality in this cohort. Studies are needed to determine whether PCSK9 inactivation promotes a protective immune response to malaria infection.
