title: Emergence of FY*A(null) in a Plasmodium vivax-endemic region of Papua New Guinea.
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.
authors.affiliation: Division of Geographic Medicine, Case Western Reserve School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106-4983, USA. paz@po.cwru.edu
authors.forename: P A
authors.initials: PA
authors.lastname: Zimmerman
authors.forename: I
authors.initials: I
authors.lastname: Woolley
authors.forename: G L
authors.initials: GL
authors.lastname: Masinde
authors.forename: S M
authors.initials: SM
authors.lastname: Miller
authors.forename: D T
authors.initials: DT
authors.lastname: McNamara
authors.forename: F
authors.initials: F
authors.lastname: Hazlett
authors.forename: C S
authors.initials: CS
authors.lastname: Mgone
authors.forename: M P
authors.initials: MP
authors.lastname: Alpers
authors.forename: B
authors.initials: B
authors.lastname: Genton
authors.forename: B A
authors.initials: BA
authors.lastname: Boatin
authors.forename: J W
authors.initials: JW
authors.lastname: Kazura
mesh_terms: D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary; D004375:Duffy Blood-Group System / Q000235:genetics*; D019353:Endemic Diseases; D005434:Flow Cytometry; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D016780:Malaria, Vivax / Q000453:epidemiology / Q000235:genetics*; D008969:Molecular Sequence Data; D010219:Papua New Guinea / Q000453:epidemiology; D010966:Plasmodium vivax
chemical_list: D018076:DNA, Complementary; D004375:Duffy Blood-Group System