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...
Main Authors: | , , , , , , , , , |
---|---|
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 |
id |
doaj-7c4c1486f9ea40b4968454aa740149d5 |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT brightadu polymorphismsinthernase3geneareassociatedwithsusceptibilitytocerebralmalariainghanaianchildren AT danieldodoo polymorphismsinthernase3geneareassociatedwithsusceptibilitytocerebralmalariainghanaianchildren AT selormeadukpo polymorphismsinthernase3geneareassociatedwithsusceptibilitytocerebralmalariainghanaianchildren AT benagyan polymorphismsinthernase3geneareassociatedwithsusceptibilitytocerebralmalariainghanaianchildren AT paulalhedley polymorphismsinthernase3geneareassociatedwithsusceptibilitytocerebralmalariainghanaianchildren AT bamenlagoka polymorphismsinthernase3geneareassociatedwithsusceptibilitytocerebralmalariainghanaianchildren AT georgeoadjei polymorphismsinthernase3geneareassociatedwithsusceptibilitytocerebralmalariainghanaianchildren AT severinolarsen polymorphismsinthernase3geneareassociatedwithsusceptibilitytocerebralmalariainghanaianchildren AT michaelchristiansen polymorphismsinthernase3geneareassociatedwithsusceptibilitytocerebralmalariainghanaianchildren AT michaeltheisen polymorphismsinthernase3geneareassociatedwithsusceptibilitytocerebralmalariainghanaianchildren |
_version_ |
1724733622929326080 |