| 2008 |
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| A functional single-nucleotide polymorphism in the CR1 promoter region contributes to
protection against cerebral malaria. |
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| Teeranaipong, P., Ohashi, J., Patarapotikul, J., Kimura, R., Nuchnoi, P., Hananantachai, H., Naka,
I., Putaporntip, C., Jongwutiwes, S., and Tokunaga, K. |
| |
| Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo,
Japan |
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| 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 |
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| Published in:J.Infect.Dis. 198[12], 1880-1891. 15-12-2008. |
