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Title: A functional single-nucleotide polymorphism in the CR1 promoter region contributes to protection against cerebral malaria
Authors: Phairote Teeranaipong
Jun Ohashi
Jintana Patarapotikul
Ryosuke Kimura
Pornlada Nuchnoi
Hathairad Hananantachai
Izumi Naka
Chaturong Putaporntip
Somchai Jongwutiwes
Katsushi Tokunaga
University of Tokyo
Tokai University School of Medicine
Mahidol University
Chulalongkorn University
Naresuan University
University of Tsukuba
Keywords: Medicine
Issue Date: 15-Dec-2008
Citation: Journal of Infectious Diseases. Vol.198, No.12 (2008), 1880-1891
Abstract: Background. Although the level of erythrocyte complement receptor type 1 (E-CR1) expression in patients with malaria has been extensively studied, whether the level of expression of E-CR1 is associated with severe malaria remains controversial. The present study examined a possible association of polymorphisms in the CR1 gene with the severity of malaria, and it evaluated the influence of the associated polymorphism on expression of E-CR1. Methods. Seventeen single-nucleotide polymorphisms in CR1 were genotyped in 477 Thai patients who had Plasmodium falciparum malaria (203 had mild malaria, 165 had noncerebral severe malaria, and 109 had cerebral malaria). The E-CR1 expression level was measured by flow cytometry in 24 healthy Thai subjects. Results. The T allele of the reference single-nucleotide polymorphism rs9429942 in the CR1 promoter region was strongly associated with protection against cerebral malaria (2.2% of patients with mild malaria vs. 7.8% of patients with cerebral malaria; P = .0009; Bonferroni-adjusted Pc= .0306). The E-CR1 expression level was significantly higher in individuals with the TT genotype of rs9429942 than in individuals with the TC genotype of rs9429942 (P = .0282). Conclusions. We identified a CR1 promoter allele, associated with higher E-CR1 expression, that conferred protection against cerebral malaria. Previous studies have shown that the rate of clearance of immune complexes (ICs) from the circulation is related to the E-CR1 level. These results lead to the hypothesis that the clearance of ICs regulated by E-CR1 therefore plays a crucial role in the pathogenesis of cerebral malaria. © 2008 by the Infectious Diseases Society of America. All rights reserved.
ISSN: 00221899
Appears in Collections:Scopus 2006-2010

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