title: Glycophorin C (Gerbich antigen blood group) and band 3 polymorphisms in two malaria holoendemic regions of Papua New Guinea.
abstract: The geographic overlap between the prevalence of erythrocyte polymorphisms and malaria endemicity is thought to be an example of natural selection on human populations. In Papua New Guinea (PNG), the Gerbich-negative phenotype is caused by an exon 3 deletion in the glycophorin C gene (GYPCDeltaex3) while heterozygosity for a 27-base pair deletion in the SLC4A1 gene (anion exchanger 1 or erythrocyte membrane protein, band 3), SLC4A1Delta27, results in Southeast Asian ovalocytosis. Two geographically and ethnically distinct malaria endemic regions of PNG (the Wosera [East Sepik Province] and Liksul [Madang Province]) were studied to illustrate the distribution of two prominent deletion polymorphisms (GYPCDeltaex3 and SLC4A1Delta27) and to determine if the genetic load associated with SLC4A1Delta27 would constrain independent assortment of GYPCDeltaex3 heterozygous and homozygous genotypes. The frequency of the GYPCDeltaex3 allele was higher in the Wosera (0.463) than Liksul (0.176) (chi(2); P < 0.0001). Conversely, the frequency of the SLC4A1Delta27 allele was higher in Liksul (0.0740) than the Wosera (0.0005) (chi(2); P < 0.0001). No individuals were homozygous for SLC4A1Delta27. In 355 Liksul residents, independent assortment of these two deletion polymorphisms resulted in 14 SLC4A1Delta27 carriers heterozygous for GYPCDeltaex3 and one SLC4A1Delta27 carrier homozygous for GYPCDeltaex3 (Fisher's exact test; P = 0.8040). While homozygosity for SLC4A1Delta27 appears to be nonviable, the GYPCDeltaex3 allele is not lethal when combined with SLC4A1Delta27. Neither mutation was associated with altered susceptibility to asymptomatic Plasmodium falciparum or P. vivax infection. While these erythrocyte polymorphisms apparently have no effect on blood-stage malaria infection, their contribution to susceptibility to clinical malaria morbidity requires further study.
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio 44106, USA. sheral.patel@case.edu
authors.forename: Sheral S
authors.initials: SS
authors.lastname: Patel
authors.forename: Christopher L
authors.initials: CL
authors.lastname: King
authors.forename: Charles S
authors.initials: CS
authors.lastname: Mgone
authors.forename: James W
authors.initials: JW
authors.lastname: Kazura
authors.forename: Peter A
authors.initials: PA
authors.lastname: Zimmerman
mesh_terms: D000483:Alleles; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics*; D003430:Cross-Sectional Studies; D003710:Demography; D004612:Elliptocytosis, Hereditary / Q000235:genetics; D019353:Endemic Diseases; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006021:Glycophorins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008288:Malaria / Q000453:epidemiology* / Q000235:genetics*; D010219:Papua New Guinea / Q000453:epidemiology; D011110:Polymorphism, Genetic
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D006021:Glycophorins