Genetic variants of RNASE3 (ECP) and susceptibility to severe malaria in Senegalese population
Abstract Background Severe forms of malaria (SM) are an outcome of Plasmodium falciparum infection and can cause death especially in children under 4 years of age. RNASE3 (ECP) has been identified as an inhibitor of Plasmodium parasites growth in vitro, and genetic analysis in hospitalized Ghanaian...
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| Format: | Article |
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BMC
2018-02-01
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| Series: | Malaria Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s12936-018-2205-9 |
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| author | Gora Diop Céline Derbois Cheikh Loucoubar Babacar Mbengue Bineta Niakhana Ndao Fatou Thiam Alassane Thiam Rokhaya Ndiaye Yakhya Dieye Robert Olaso Jean-Francois Deleuze Alioune Dieye |
| author_facet | Gora Diop Céline Derbois Cheikh Loucoubar Babacar Mbengue Bineta Niakhana Ndao Fatou Thiam Alassane Thiam Rokhaya Ndiaye Yakhya Dieye Robert Olaso Jean-Francois Deleuze Alioune Dieye |
| author_sort | Gora Diop |
| collection | DOAJ |
| description | Abstract Background Severe forms of malaria (SM) are an outcome of Plasmodium falciparum infection and can cause death especially in children under 4 years of age. RNASE3 (ECP) has been identified as an inhibitor of Plasmodium parasites growth in vitro, and genetic analysis in hospitalized Ghanaian subjects has revealed the RNASE3 +371G/C (rs2073342) polymorphism as a susceptibility factor for cerebral malaria. The +371 C allele results in an Arg/Thr mutation that abolishes the cytotoxic activity of the ECP protein. The present study aims to investigate RNASE3 gene polymorphisms and their putative link to severe malaria in a malaria cohort from Senegal. Methods/results Patients enrolled from hospitals were classified as having either uncomplicated (UM) or severe malaria (SM). The analysis of the RNASE3 gene polymorphisms was performed in 241 subjects: 178 falciparum infected (96 SM, 82 UM) and 63 non-infected subjects as population control group (CTR). Six frequent SNPs (MAF > 3%) were identified, and one SNP was associated with malaria severity by performing a logistic regression analysis SM vs.UM: RNASE3 +499G/C (rs2233860) under age, sex as covariates and HbS/HbC polymorphisms adjustment (p = 0.003, OR 0.43, CI 95% 0.20–0.92). The polymorphisms: +371G/C (rs2073342), +499G/C (rs2233860) and +577A/T (rs8019343) defined a haplotype risk (G-G-T) for malaria severity (Fisher exact test, p = 0.03) (OR 4.1, IC 95% (1.1–14.9). Conclusion In addition to the previously described association of +371G/C polymorphism in Ghanaians cohort, the RNASE3 +499G/C polymorphism was associated with susceptibility to SM in a Senegalese population. The haplotype +371G/+499G/+577T defined by RNASE3 polymorphisms was associated with severity. The genetic association identified independently in the Senegalese population provide additional evidence of a role of RNASE3 (ECP) in malaria severity. |
| first_indexed | 2024-12-11T16:43:11Z |
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| id | doaj.art-ed5cfb85490a483683c263f98fba2dbd |
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| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-11T16:43:11Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
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| series | Malaria Journal |
| spelling | doaj.art-ed5cfb85490a483683c263f98fba2dbd2022-12-22T00:58:16ZengBMCMalaria Journal1475-28752018-02-0117111010.1186/s12936-018-2205-9Genetic variants of RNASE3 (ECP) and susceptibility to severe malaria in Senegalese populationGora Diop0Céline Derbois1Cheikh Loucoubar2Babacar Mbengue3Bineta Niakhana Ndao4Fatou Thiam5Alassane Thiam6Rokhaya Ndiaye7Yakhya Dieye8Robert Olaso9Jean-Francois Deleuze10Alioune Dieye11Faculté des Sciences et Techniques, Département de Biologie animale, Unité postulante de Biologie Génétique, Génomique et Bioinformatique (G2B), Université Cheikh Anta DIOP de Dakar, UCADUnité de Moyen-bas Débit, Institut de Génomique-CEA, Centre National de Recherche en Génomique HumaineGroupe G4, Biostatistique et Bioinformatique, Institut Pasteur de DakarUnité d’Immunogénétique, Institut Pasteur de DakarFaculté des Sciences et Techniques, Département de Biologie animale, Unité postulante de Biologie Génétique, Génomique et Bioinformatique (G2B), Université Cheikh Anta DIOP de Dakar, UCADUnité d’Immunogénétique, Institut Pasteur de DakarUnité d’Immunogénétique, Institut Pasteur de DakarUnité d’Immunogénétique, Institut Pasteur de DakarDépartement de Génie chimique et Biologie appliquée, Ecole Supérieure Polytechnique, Université Cheikh Anta DIOP de Dakar, UCADUnité de Moyen-bas Débit, Institut de Génomique-CEA, Centre National de Recherche en Génomique HumaineUnité de Moyen-bas Débit, Institut de Génomique-CEA, Centre National de Recherche en Génomique HumaineUnité d’Immunogénétique, Institut Pasteur de DakarAbstract Background Severe forms of malaria (SM) are an outcome of Plasmodium falciparum infection and can cause death especially in children under 4 years of age. RNASE3 (ECP) has been identified as an inhibitor of Plasmodium parasites growth in vitro, and genetic analysis in hospitalized Ghanaian subjects has revealed the RNASE3 +371G/C (rs2073342) polymorphism as a susceptibility factor for cerebral malaria. The +371 C allele results in an Arg/Thr mutation that abolishes the cytotoxic activity of the ECP protein. The present study aims to investigate RNASE3 gene polymorphisms and their putative link to severe malaria in a malaria cohort from Senegal. Methods/results Patients enrolled from hospitals were classified as having either uncomplicated (UM) or severe malaria (SM). The analysis of the RNASE3 gene polymorphisms was performed in 241 subjects: 178 falciparum infected (96 SM, 82 UM) and 63 non-infected subjects as population control group (CTR). Six frequent SNPs (MAF > 3%) were identified, and one SNP was associated with malaria severity by performing a logistic regression analysis SM vs.UM: RNASE3 +499G/C (rs2233860) under age, sex as covariates and HbS/HbC polymorphisms adjustment (p = 0.003, OR 0.43, CI 95% 0.20–0.92). The polymorphisms: +371G/C (rs2073342), +499G/C (rs2233860) and +577A/T (rs8019343) defined a haplotype risk (G-G-T) for malaria severity (Fisher exact test, p = 0.03) (OR 4.1, IC 95% (1.1–14.9). Conclusion In addition to the previously described association of +371G/C polymorphism in Ghanaians cohort, the RNASE3 +499G/C polymorphism was associated with susceptibility to SM in a Senegalese population. The haplotype +371G/+499G/+577T defined by RNASE3 polymorphisms was associated with severity. The genetic association identified independently in the Senegalese population provide additional evidence of a role of RNASE3 (ECP) in malaria severity.http://link.springer.com/article/10.1186/s12936-018-2205-9Severe malariaPlasmodium falciparumSusceptibilityRNase3 (ECP) genePolymorphismsSenegal |
| spellingShingle | Gora Diop Céline Derbois Cheikh Loucoubar Babacar Mbengue Bineta Niakhana Ndao Fatou Thiam Alassane Thiam Rokhaya Ndiaye Yakhya Dieye Robert Olaso Jean-Francois Deleuze Alioune Dieye Genetic variants of RNASE3 (ECP) and susceptibility to severe malaria in Senegalese population Malaria Journal Severe malaria Plasmodium falciparum Susceptibility RNase3 (ECP) gene Polymorphisms Senegal |
| title | Genetic variants of RNASE3 (ECP) and susceptibility to severe malaria in Senegalese population |
| title_full | Genetic variants of RNASE3 (ECP) and susceptibility to severe malaria in Senegalese population |
| title_fullStr | Genetic variants of RNASE3 (ECP) and susceptibility to severe malaria in Senegalese population |
| title_full_unstemmed | Genetic variants of RNASE3 (ECP) and susceptibility to severe malaria in Senegalese population |
| title_short | Genetic variants of RNASE3 (ECP) and susceptibility to severe malaria in Senegalese population |
| title_sort | genetic variants of rnase3 ecp and susceptibility to severe malaria in senegalese population |
| topic | Severe malaria Plasmodium falciparum Susceptibility RNase3 (ECP) gene Polymorphisms Senegal |
| url | http://link.springer.com/article/10.1186/s12936-018-2205-9 |
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