Polymorphisms in the RNASE3 Gene Are Associated with Susceptibility to Cerebral Malaria in Ghanaian Children
Date
2011-12
Journal Title
Journal ISSN
Volume Title
Publisher
PLOS
Abstract
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.
Description
The orginal article is available at www.plos.org
Keywords
Cerebral malaria in children -- Ghana, Plasmodium falciparum infection -- Prevention -- Ghana, Eosinophilia, Eosinophil cationic protein, Eosinophil disorders
Citation
Adu 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): e29465