Polymorphisms in the RNASE3 gene are associated with susceptibility to cerebral malaria in Ghanaian children.

BACKGROUND: Cerebral malaria (CM) is the most severe outcome of Plasmodium falciparum infection and a major cause of death in children from 2 to 4 years of age. A hospital based study in Ghana showed that P. falciparum induces eosinophilia and found a significantly higher serum level of eosinophil c...

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Main Authors: Bright Adu, Daniel Dodoo, Selorme Adukpo, Ben A Gyan, Paula L Hedley, Bamenla Goka, George O Adjei, Severin O Larsen, Michael Christiansen, Michael Theisen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3246477?pdf=render
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spelling doaj-7c4c1486f9ea40b4968454aa740149d52020-11-25T02:51:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01612e2946510.1371/journal.pone.0029465Polymorphisms in the RNASE3 gene are associated with susceptibility to cerebral malaria in Ghanaian children.Bright AduDaniel DodooSelorme AdukpoBen A GyanPaula L HedleyBamenla GokaGeorge O AdjeiSeverin O LarsenMichael ChristiansenMichael TheisenBACKGROUND: Cerebral malaria (CM) is the most severe outcome of Plasmodium falciparum infection and a major cause of death in children from 2 to 4 years of age. A hospital based study in Ghana showed that P. falciparum induces eosinophilia and found a significantly higher serum level of eosinophil cationic protein (ECP) in CM patients than in uncomplicated malaria (UM) and severe malaria anemia (SA) patients. Single nucleotide polymorphisms (SNPs) have been described in the ECP encoding-gene (RNASE3) of which the c.371G>C polymorphism (rs2073342) results in an arginine to threonine amino acid substitution p.R124T in the polypeptide and abolishes the cytotoxicity of ECP. The present study aimed to investigate the potential association between polymorphisms in RNASE3 and CM. METHODOLOGY/PRINCIPAL FINDINGS: The RNASE3 gene and flanking regions were sequenced in 206 Ghanaian children enrolled in a hospital based malaria study. An association study was carried out to assess the significance of five SNPs in CM (n=45) and SA (n=56) cases, respectively. The two severe case groups (CM and SA) were compared with the non-severe control group comprising children suffering from UM (n=105). The 371G allele was significantly associated with CM (p=0.00945, OR=2.29, 95% CI=1.22-4.32) but not with SA. Linkage disequilibrium analysis demonstrated significant linkage between three SNPs and the haplotype combination 371G/*16G/*94A was strongly associated with susceptibility to CM (p=0.000913, OR=4.14, 95% CI=1.79-9.56), thus, defining a risk haplotype. The RNASE3 371GG genotype was found to be under frequency-dependent selection. CONCLUSIONS/SIGNIFICANCE: The 371G allele of RNASE3 is associated with susceptibility to CM and forms part of a risk associated haplotype GGA defined by the markers: rs2073342 (G-allele), rs2233860 (G-allele) and rs8019343 (A-allele) respectively. Collectively, these results suggest a hitherto unrecognized role for eosinophils in CM pathogenesis.http://europepmc.org/articles/PMC3246477?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Bright Adu
Daniel Dodoo
Selorme Adukpo
Ben A Gyan
Paula L Hedley
Bamenla Goka
George O Adjei
Severin O Larsen
Michael Christiansen
Michael Theisen
spellingShingle Bright Adu
Daniel Dodoo
Selorme Adukpo
Ben A Gyan
Paula L Hedley
Bamenla Goka
George O Adjei
Severin O Larsen
Michael Christiansen
Michael Theisen
Polymorphisms in the RNASE3 gene are associated with susceptibility to cerebral malaria in Ghanaian children.
PLoS ONE
author_facet Bright Adu
Daniel Dodoo
Selorme Adukpo
Ben A Gyan
Paula L Hedley
Bamenla Goka
George O Adjei
Severin O Larsen
Michael Christiansen
Michael Theisen
author_sort Bright Adu
title Polymorphisms in the RNASE3 gene are associated with susceptibility to cerebral malaria in Ghanaian children.
title_short Polymorphisms in the RNASE3 gene are associated with susceptibility to cerebral malaria in Ghanaian children.
title_full Polymorphisms in the RNASE3 gene are associated with susceptibility to cerebral malaria in Ghanaian children.
title_fullStr Polymorphisms in the RNASE3 gene are associated with susceptibility to cerebral malaria in Ghanaian children.
title_full_unstemmed Polymorphisms in the RNASE3 gene are associated with susceptibility to cerebral malaria in Ghanaian children.
title_sort polymorphisms in the rnase3 gene are associated with susceptibility to cerebral malaria in ghanaian children.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2011-01-01
description BACKGROUND: Cerebral malaria (CM) is the most severe outcome of Plasmodium falciparum infection and a major cause of death in children from 2 to 4 years of age. A hospital based study in Ghana showed that P. falciparum induces eosinophilia and found a significantly higher serum level of eosinophil cationic protein (ECP) in CM patients than in uncomplicated malaria (UM) and severe malaria anemia (SA) patients. Single nucleotide polymorphisms (SNPs) have been described in the ECP encoding-gene (RNASE3) of which the c.371G>C polymorphism (rs2073342) results in an arginine to threonine amino acid substitution p.R124T in the polypeptide and abolishes the cytotoxicity of ECP. The present study aimed to investigate the potential association between polymorphisms in RNASE3 and CM. METHODOLOGY/PRINCIPAL FINDINGS: The RNASE3 gene and flanking regions were sequenced in 206 Ghanaian children enrolled in a hospital based malaria study. An association study was carried out to assess the significance of five SNPs in CM (n=45) and SA (n=56) cases, respectively. The two severe case groups (CM and SA) were compared with the non-severe control group comprising children suffering from UM (n=105). The 371G allele was significantly associated with CM (p=0.00945, OR=2.29, 95% CI=1.22-4.32) but not with SA. Linkage disequilibrium analysis demonstrated significant linkage between three SNPs and the haplotype combination 371G/*16G/*94A was strongly associated with susceptibility to CM (p=0.000913, OR=4.14, 95% CI=1.79-9.56), thus, defining a risk haplotype. The RNASE3 371GG genotype was found to be under frequency-dependent selection. CONCLUSIONS/SIGNIFICANCE: The 371G allele of RNASE3 is associated with susceptibility to CM and forms part of a risk associated haplotype GGA defined by the markers: rs2073342 (G-allele), rs2233860 (G-allele) and rs8019343 (A-allele) respectively. Collectively, these results suggest a hitherto unrecognized role for eosinophils in CM pathogenesis.
url http://europepmc.org/articles/PMC3246477?pdf=render
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