Journal Article

A Functional Single-Nucleotide Polymorphism in the CR1 Promoter Region Contributes to Protection against Cerebral Malaria

Phairote Teeranaipong, Jun Ohashi, Jintana Patarapotikul, Ryosuke Kimura, Pornlada Nuchnoi, Hathairad Hananantachai, Izumi Naka, Chaturong Putaporntip, Somchai Jongwutiwes and Katsushi Tokunaga

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 198, issue 12, pages 1880-1891
Published in print December 2008 | ISSN: 0022-1899
Published online December 2008 | e-ISSN: 1537-6613 | DOI: https://dx.doi.org/10.1086/593338
A Functional Single-Nucleotide Polymorphism in the CR1 Promoter Region Contributes to Protection against Cerebral Malaria

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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.

Journal Article.  4839 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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