Emergence of FY*A(null) in a Plasmodium vivax-endemic region of Papua New Guinea

Details

Serval ID
serval:BIB_A2541037AB49
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Emergence of FY*A(null) in a Plasmodium vivax-endemic region of Papua New Guinea
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Zimmerman  P. A., Woolley  I., Masinde  G. L., Miller  S. M., McNamara  D. T., Hazlett  F., Mgone  C. S., Alpers  M. P., Genton  B., Boatin  B. A., Kazura  J. W.
ISSN
0027-8424 (Print)
Publication state
Published
Issued date
11/1999
Volume
96
Number
24
Pages
13973-7
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Nov 23
Abstract
In Papua New Guinea (PNG), numerous blood group polymorphisms and hemoglobinopathies characterize the human population. Human genetic polymorphisms of this nature are common in malarious regions, and all four human malaria parasites are holoendemic below 1500 meters in PNG. At this elevation, a prominent condition characterizing Melanesians is alpha(+)-thalassemia. Interestingly, recent epidemiological surveys have demonstrated that alpha(+)-thalassemia is associated with increased susceptibility to uncomplicated malaria among young children. It is further proposed that alpha(+)-thalassemia may facilitate so-called "benign" Plasmodium vivax infection to act later in life as a "natural vaccine" against severe Plasmodium falciparum malaria. Here, in a P. vivax-endemic region of PNG where the resident Abelam-speaking population is characterized by a frequency of alpha(+)-thalassemia >/=0.98, we have discovered the mutation responsible for erythrocyte Duffy antigen-negativity (Fy[a-b-]) on the FY*A allele. In this study population there were 23 heterozygous and no homozygous individuals bearing this new allele (allele frequency, 23/1062 = 0.022). Flow cytometric analysis illustrated a 2-fold difference in erythroid-specific Fy-antigen expression between heterozygous (FY*A/FY*A(null)) and homozygous (FY*A/FY*A) individuals, suggesting a gene-dosage effect. In further comparisons, we observed a higher prevalence of P. vivax infection in FY*A/FY*A (83/508 = 0.163) compared with FY*A/FY*A(null) (2/23 = 0.087) individuals (odds ratio = 2.05, 95% confidence interval = 0.47-8.91). Emergence of FY*A(null) in this population suggests that P. vivax is involved in selection of this erythroid polymorphism. This mutation would ultimately compromise alpha(+)-thalassemia/P. vivax-mediated protection against severe P. falciparum malaria.
Keywords
Animals Base Sequence DNA, Complementary Duffy Blood-Group System/*genetics *Endemic Diseases Flow Cytometry Gene Expression Genotype Humans Malaria, Vivax/epidemiology/*genetics Molecular Sequence Data Papua New Guinea/epidemiology Plasmodium vivax
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:48
Last modification date
20/08/2019 15:08
Usage data