Emergence of FYA super(null) in a Plasmodium vivax-endemic region of Papua New Guinea

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 24; pp. 13973 - 13977
• Main Authors: 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, BA, Kazura, J W
• Format: Journal Article
• Language: English
• Published: 23.11.1999
• Subjects: a-thalassemia; Papua New Guinea; Plasmodium vivax; population genetics
• ISSN: 0027-8424
• DOI: 10.1073/pnas.96.24.13973

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 super(+)-thalassemia. Interestingly, recent epidemiological surveys have demonstrated that alpha super(+)-thalassemia is associated with increased susceptibility to uncomplicated malaria among young children. It is further proposed that alpha super(+)-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 super(+)- thalassemia greater than or equal to 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 super(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 super(null) (2/23 = 0.087) individuals (odds ratio = 2.05, 95% confidence interval = 0.47-8.91). Emergence of FY*A super(null) in this population suggests that P. vivax is involved in selection of this erythroid polymorphism. This mutation would ultimately compromise alpha super(+)-thalassemia/P. vivax-mediated protection against severe P. falciparum malaria.