Research Article Association of the rs562556 PCSK9 Gene Polymorphism with Reduced Mortality in Severe Malaria among Malian Children Olesya Fedoryak, 1,2 Charles Arama, 3 Issa Diarra, 3 Bour´ ema Kouriba, 3 Michel Chr´ etien, 1,4 and Majambu Mbikay 1,4 1 Functional Endoproteolysis Laboratory, Clinical Research Institute of Montreal, Montreal H2W 1R7, Quebec, Canada 2 Department of Chemistry, Faculty of Sciences, University of Manitoba, Winnipeg R3T 2N2, Manitoba, Canada 3 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, Bamako, Mali 4 Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa K1H 8L6, Ontario, Canada Correspondence should be addressed to Majambu Mbikay; majambu.mbikay@ircm.qc.ca Received 13 June 2020; Revised 31 August 2020; Accepted 10 September 2020; Published 24 September 2020 Academic Editor: Mario Dell Agli Copyright © 2020 Olesya Fedoryak et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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.1420A > 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. In- triguingly, 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. 1. Introduction Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a liver-secreted protein that binds the low-density lipoprotein receptor (LDLR) at the surface of hepatocytes and escorts it inside the cells towards lysosomes where it gets degraded. It thus reduces LDLR-mediated hepatic uptake of plasma LDL- cholesterol (LDL-C), causing its accumulation in the bloodstream. Single nucleotide polymorphisms (SNPs) in the human PCSK9 gene have been associated with either hypercholesterolemia or hypocholesterolemia, depending on whether they increase (gain-of-function, GOF) or reduce (loss-of-function, LOF) PCSK9 activity [1]. Recent evidence suggests that PCSK9 can modulate the immune response to infection, favorably when less active and deleteriously when overactive [2]. We wanted to verify whether PCSK9 could influence the course of malaria infection. One step to that end is to de- termine how common GOF and LOF genetic variations segregate with the severity and the outcome of the disease. We previously reported an association of the GOF PCSK9 SNP rs505151 (c.2009A > G, p.E670 G) with severe malaria in Malian children [3]. Using the same cohort, here we investigate the possible association the LOF SNP rs562556 (c.1420A > G, p.I474 V) with malaria mortality. 2. Subjects and Methods 2.1.StudySubjects. Subjects of the present study were 3-month to 14-year-old children diagnosed with severe malaria. ey were participants in a previous case-control study investigating physiological factors that increase or decrease the risk for severe Hindawi Canadian Journal of Infectious Diseases and Medical Microbiology Volume 2020, Article ID 9340480, 5 pages https://doi.org/10.1155/2020/9340480