Abstract
BackgroundThe complex interactions between the human host and the Plasmodium falciparum parasite and the factors influencing severity of disease are still not fully understood. Human single nucleotide polymorphisms SNPs associated with Knops blood group system; carried by complement receptor 1 may be associated with the pathology of P. falciparum malaria, and susceptibility to disease.MethodsThe objective of this study was to determine the genotype and haplotype frequencies of the SNPs defining the Knops blood group antigens; Kna/b, McCoya/b, Swain-Langley1/2 and KCAM+/- in Ghanaian patients with malaria and determine possible associations between these polymorphisms and the severity of the disease. Study participants were patients (n = 267) admitted to the emergency room at the Department of Child Health, Korle-Bu Teaching Hospital, Accra, Ghana during the malaria season from June to August in 1995, 1996 and 1997, classified as uncomplicated malaria (n = 89), severe anaemia (n = 57) and cerebral malaria (n = 121) and controls who did not have a detectable Plasmodium infection or were symptomless carriers of the parasite (n = 275). The frequencies were determined using a post-PCR ligation detection reaction-fluorescent microsphere assay, developed to detect the SNPs defining the antigens. Chi-square/Fisher’s exact test and logistic regression models were used to analyse the data.ResultsAs expected, high frequencies of the alleles Kna, McCb, Sl2 and KCAM- were found in the Ghanaian population. Apart from small significant differences between the groups at the Sl locus, no significant allelic or genotypic differences were found between the controls and the disease groups or between the disease groups. The polymorphisms define eight different haplotypes H1(2.4%), H2(9.4%), H3(59.8%), H4(0%), H5(25.2%), H6(0.33%), H7(2.8%) and H8(0%). Investigating these haplotypes, no significant differences between any of the groups were found.ConclusionThe results confirm earlier findings of high frequencies of certain CR1 alleles in Africa; and shed more light on earlier conflicting findings; the alleles McCb, Sl2, Knb and KCAM- or combined haplotypes do not seem to confer any protective advantage against malaria infection or resulting disease severity. Based on these findings, in a very well-characterized population, malaria does not seem to be the selective force on these alleles.
Highlights
The complex interactions between the human host and the Plasmodium falciparum parasite and the factors influencing severity of disease are still not fully understood
No significant differences were observed in the mean age or the proportion of males between the control and disease groups except for the severe anaemia group where the mean age was lower than controls (P = 0.93 ) and the proportion of males was higher than controls (P = 0.02) (Table 2)
Allele and genotype frequencies at the Knops antigen (Kn) McC, Sl and KCAM loci in the disease and control groups The capacity of the Luminex technique to correctly detect the single nucleotide polymorphism (SNP) at the Kn, McC, Sl and KCAM loci was tested by use of control DNA samples from individuals with known genotypes
Summary
The complex interactions between the human host and the Plasmodium falciparum parasite and the factors influencing severity of disease are still not fully understood. Human single nucleotide polymorphisms SNPs associated with Knops blood group system; carried by complement receptor 1 may be associated with the pathology of P. falciparum malaria, and susceptibility to disease. The complex interactions between the human host and Plasmodium falciparum and the factors influencing severity of disease are still not fully understood. The potential role of CR1 in the severity of malaria seems plausible since it has been shown that CR1 is involved in rosetting by binding to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) [5]
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