Reduced Risk of Plasmodium vivax Malaria in Papua New Guinean Children with Southeast Asian Ovalocytosis in Two Cohorts and a Case-Control Study
The high frequencies of mutant haemoglobin and erythrocyte surface proteins in malaria-endemic regions have indicated that polymorphisms in human genes have been under selection pressure by severe malarial disease. Glycophorin C (GYPC) is a major surface erythrocyte protein and also a receptor for the Plasmodium falciparum erythrocyte-binding antigen 140 (EBA-140, also known as BAEBL). There is no binding to GYPC in Gerbich-negative (deletion of exon 3 in GYPC gene: GYPCC delta(exon3)) erythrocytes by EBA-140, hence limiting invasion of erythrocytes by certain P. falciparum lines. The GYPCC delta(exon3) allele reaches high frequencies in two areas of Papua New Guinea (PNG) where malaria is highly endemic. There is, however, no indication that Gerbich negativity protects against malaria-related illness. Using archival blood samples collected from children (<6 years of age) in the Wosera District, East Sepik Province, PNG, we investigated GYPC C delta(exon3) as a possible genetic component of protection against severe malarial anaemia (SMA). The frequency of this human genetic polymorphism was found to be in accordance with previous studies. However, our result showed no association between SMA and GYPC C delta(exon3). Until such an association is clearly shown with severe malaria outcomes, these results raise questions regarding the role of malaria as a selective force for Gerbich negativity.