CR1 Knops blood group alleles are not associated with severe malaria in the Gambia - PubMed (original) (raw)

CR1 Knops blood group alleles are not associated with severe malaria in the Gambia

P A Zimmerman et al. Genes Immun. 2003 Jul.

Abstract

The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-value <0.05). Given the role of CR1 in host defense, our findings suggest that Sl 2 and McC(b) have arisen to confer a selective advantage against infectious disease that, in view of these case-control study data, was not solely Plasmodium falciparum malaria. Factors underlying the lack of association between Sl 2 and McC(b) with severe malaria may involve variation in CR1 expression levels.

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Figures

Figure 1

Figure 1

Amino-acid sequence alignment comparing CR1CCP25 (Hs) alleles. Standard single-letter nomenclature illustrates the amino-acid sequence for five human CR1CCP25 alleles. This sequence is inclusive of amino acids 1587–1648. Amino-acid identity is represented by a dash (-); polymorphic positions are identified by a variant amino-acid symbol compared to the CR1CCP25_Hs_1 reference sequence. GenBank accession numbers for each of the human CR1CCP25 alleles include AF264716 (CRlCCP25_Hs_1), AF264715 (CR1CCP25_Hs_2), L17408 (CR1CCP25_Hs_3), AF169969 (CR1CCP25_Hs_4), and AF169970 (CR1CCP25_Hs_5).

Figure 2

Figure 2

Post-PCR ligase detection reaction (LDR) genotyping assay.

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