Association of the rs562556 PCSK9 Gene Polymorphism with Reduced Mortality in Severe Malaria among Malian Children
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.14...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Canadian Journal of Infectious Diseases and Medical Microbiology |
| Online Access: | http://dx.doi.org/10.1155/2020/9340480 |
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| author | Olesya Fedoryak Charles Arama Issa Diarra Bouréma Kouriba Michel Chrétien Majambu Mbikay |
| author_facet | Olesya Fedoryak Charles Arama Issa Diarra Bouréma Kouriba Michel Chrétien Majambu Mbikay |
| author_sort | Olesya Fedoryak |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-06126bf1ac6e4c48abff9868fc0424b9 |
| institution | Kabale University |
| issn | 1712-9532 1918-1493 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Canadian Journal of Infectious Diseases and Medical Microbiology |
| spelling | doaj-art-06126bf1ac6e4c48abff9868fc0424b92025-02-03T01:04:28ZengWileyCanadian Journal of Infectious Diseases and Medical Microbiology1712-95321918-14932020-01-01202010.1155/2020/93404809340480Association of the rs562556 PCSK9 Gene Polymorphism with Reduced Mortality in Severe Malaria among Malian ChildrenOlesya Fedoryak0Charles Arama1Issa Diarra2Bouréma Kouriba3Michel Chrétien4Majambu Mbikay5Functional Endoproteolysis Laboratory, Clinical Research Institute of Montreal, Montreal H2W 1R7, Quebec, CanadaMalaria 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, MaliMalaria 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, MaliMalaria 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, MaliFunctional Endoproteolysis Laboratory, Clinical Research Institute of Montreal, Montreal H2W 1R7, Quebec, CanadaFunctional Endoproteolysis Laboratory, Clinical Research Institute of Montreal, Montreal H2W 1R7, Quebec, CanadaRecent 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.http://dx.doi.org/10.1155/2020/9340480 |
| spellingShingle | Olesya Fedoryak Charles Arama Issa Diarra Bouréma Kouriba Michel Chrétien Majambu Mbikay Association of the rs562556 PCSK9 Gene Polymorphism with Reduced Mortality in Severe Malaria among Malian Children Canadian Journal of Infectious Diseases and Medical Microbiology |
| title | Association of the rs562556 PCSK9 Gene Polymorphism with Reduced Mortality in Severe Malaria among Malian Children |
| title_full | Association of the rs562556 PCSK9 Gene Polymorphism with Reduced Mortality in Severe Malaria among Malian Children |
| title_fullStr | Association of the rs562556 PCSK9 Gene Polymorphism with Reduced Mortality in Severe Malaria among Malian Children |
| title_full_unstemmed | Association of the rs562556 PCSK9 Gene Polymorphism with Reduced Mortality in Severe Malaria among Malian Children |
| title_short | Association of the rs562556 PCSK9 Gene Polymorphism with Reduced Mortality in Severe Malaria among Malian Children |
| title_sort | association of the rs562556 pcsk9 gene polymorphism with reduced mortality in severe malaria among malian children |
| url | http://dx.doi.org/10.1155/2020/9340480 |
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