|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 August 2002, Vol. 100, No. 4, pp. 1172-1176
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Hemoglobin E: a balanced polymorphism protective against high
parasitemias and thus severe P falciparum malaria
Kesinee Chotivanich,
Rachanee Udomsangpetch,
Kovit Pattanapanyasat,
Wirongrong Chierakul,
Julie Simpson,
Sornchai Looareesuwan, and
Nicholas White
From the Faculty of Tropical Medicine, Department of
Pathobiology, Faculty of Science, and Office for Research and
Development, Faculty of Medicine, Mahidol University, Bangkok,
Thailand; and the Nuffield Department of Medicine, John Radcliffe
Hospital, Oxford University, Oxford, United Kingdom.
Hemoglobin E is very common in parts of Southeast Asia. The
possible malaria protective effects of this and other inherited hemoglobin abnormalities prevalent in Thailand were assessed in a mixed
erythrocyte invasion assay. In vitro, starting at 1% parasitemia, Plasmodium falciparum preferentially invaded normal (HbAA)
compared to abnormal hemoglobin (HbH, AE, EE, HCS,  -thalassemia E)
red cells (HRBCs). The median (range) ratio of parasitization of HRBCs (n = 109) compared to the controls of different major blood groups was 0.40 (0.08, 0.98), less than half that of the normal red cells (NRBCs) compared to their controls 0.88 (0.53, 1.4;
P = .001). The median (range) parasitemia in the HRBCs
was 2% (0.1%-9%) compared to 5.2% (1.2%-16.3%) in the NRBCs
(P = .001). The proportion of the RBC population that is
susceptible to malaria parasite invasion can be described by a
selectivity index (SI; observed number of multiply invaded RBCs/number
predicted). The heterozygote AE cells differed markedly from all the
other cells tested with invasion restricted to approximately 25% of
the RBCs; the median (range) SI was 3.8 (1-15) compared with 0.75 (0.1-0.9) for EE RBCs (P < .01). Despite their
microcytosis, AE cells are functionally relatively normal in contrast
to the RBCs from the other hemoglobinopathies studied. These findings
suggest that HbAE erythrocytes have an unidentified membrane
abnormality that renders the majority of the RBC population relatively
resistant to invasion by P falciparum. This would not
protect from uncomplicated malaria infections but would prevent the
development of heavy parasite burdens and is consistent with the
"Haldane" hypothesis of heterozygote protection against severe
malaria for hemoglobin E.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
F. P. Mockenhaupt, J. P. Cramer, L. Hamann, M. S. Stegemann, J. Eckert, N.-R. Oh, R. N. Otchwemah, E. Dietz, S. Ehrhardt, N. W. J. Schroder, et al.
Toll-like receptor (TLR) polymorphisms in African children: Common TLR-4 variants predispose to severe malaria
PNAS,
January 3, 2006;
103(1):
177 - 182.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Tiffert, V. L. Lew, H. Ginsburg, M. Krugliak, L. Croisille, and N. Mohandas
The hydration state of human red blood cells and their susceptibility to invasion by Plasmodium falciparum
Blood,
June 15, 2005;
105(12):
4853 - 4860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ayi, F. Turrini, A. Piga, and P. Arese
Enhanced phagocytosis of ring-parasitized mutant erythrocytes: a common mechanism that may explain protection against falciparum malaria in sickle trait and beta-thalassemia trait
Blood,
November 15, 2004;
104(10):
3364 - 3371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Frodsham and A. V.S. Hill
Genetics of infectious diseases
Hum. Mol. Genet.,
October 1, 2004;
13(suppl_2):
R187 - R194.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Fairhurst, H. Fujioka, K. Hayton, K. F. Collins, and T. E. Wellems
Aberrant development of Plasmodium falciparum in hemoglobin CC red cells: implications for the malaria protective effect of the homozygous state
Blood,
April 15, 2003;
101(8):
3309 - 3315.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
