Polymorphisms in the RNASE3 Gene Are Associated with Susceptibility to Cerebral Malaria in Ghanaian Children

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dc.contributor.authorAdu, Bright
dc.contributor.authorDodoo, Daniel
dc.contributor.authorAdukpo, Selorme
dc.contributor.authorGyan, Ben A.
dc.contributor.authorHedley, Paula L.
dc.contributor.authorGoka, Bamenla
dc.contributor.authorAdjei, George O.
dc.contributor.authorLarsen, Severin O.
dc.contributor.authorChristiansen, Michael
dc.contributor.authorTheisen, Michael
dc.date.accessioned2013-03-14T14:52:58Z
dc.date.available2013-03-14T14:52:58Z
dc.date.issued2011-12
dc.descriptionThe orginal article is available at www.plos.orgen_ZA
dc.description.abstractBackground: 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.en_ZA
dc.description.sponsorshipEuropean and Developing Countries Clinical Trials Partnership (TA.2007.40200.012)
dc.description.sponsorshipMultilateral Initiative on Malaria-Training in Tropical Diseases (MIM-TDR project A11034).
dc.description.versionPublisher's versionen_ZA
dc.format.extent9 p. : ill.
dc.identifier.citationAdu B, Dodoo D, Adukpo S, Gyan BA, Hedley PL, et al. (2011) Polymorphisms in the RNASE3 Gene Are Associated with Susceptibility to Cerebral Malaria in Ghanaian Children. PLoS ONE 6(12): e29465en_ZA
dc.identifier.otherdoi:10.1371/journal.pone.0029465
dc.identifier.urihttp://hdl.handle.net/10019.1/79782
dc.language.isoen_ZAen_ZA
dc.publisherPLOSen_ZA
dc.rights.holderThe author holds the copyrighten_ZA
dc.subjectCerebral malaria in children -- Ghanaen_ZA
dc.subjectPlasmodium falciparum infection -- Prevention -- Ghanaen_ZA
dc.subjectEosinophiliaen_ZA
dc.subjectEosinophil cationic proteinen_ZA
dc.subjectEosinophil disordersen_ZA
dc.subject.lcshGenetic polymorphismsen_ZA
dc.subject.lcshCerebral malaria -- Diagnosis -- Ghanaen_ZA
dc.subject.lcshPlasmodium falciparum infection -- Diagnosis -- Ghanaen_ZA
dc.titlePolymorphisms in the RNASE3 Gene Are Associated with Susceptibility to Cerebral Malaria in Ghanaian Childrenen_ZA
dc.typeArticleen_ZA
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