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

Genes & Immunity volume 4, pages 368–373 (2003)Cite this article

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 McCa/McCb, 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, 1365/1706) and McCb (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McCa allele observed in all populations, the African Sl 2/McCb 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 McCb 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 McCb with severe malaria may involve variation in CR1 expression levels.

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Acknowledgements

We thank L Miller, AG Palmer III, M Johnson, and E Eichler for helpful discussions during this study, and B Greenwood, D Kwiatkowski, CEM Allsopp, S Bennett, and N Anstey who contributed to conduct and design of the original case–control study. Funding support was provided by the National Institutes of Health (AI R01 42367 (JMM) and the Wellcome Trust (AVSH is a Wellcome Trust Principal Research Fellow and 055167 (JAR)).

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Authors and Affiliations

  1. The Center for Global Health & Diseases, Case Western Reserve University, School of Medicine, Cleveland, 44106-4983, OH, USA

    P A Zimmerman, D T McNamara & L J Kasehagen

  2. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK

    J Fitness & A V S Hill

  3. Department of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, 19129-1096, PA, USA

    J M Moulds

  4. Institute of Cell, Animal and Population Biology, University of Edinburgh, King's Buildings, West Mains Rd, Edinburgh, EH9 3JT, UK

    J Alexandra Rowe

  5. MRC Laboratories, PO Box 273, Fajara, The Gambia

    A V S Hill

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  1. P A Zimmerman
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Correspondence to P A Zimmerman.

Additional information

Nomenclature for the Knops blood group Swain–Langley has been updated at the International Society of Blood Transfusion Nomenclature Committee meeting, 27th Congress of the ISBT, Vancouver, British Columbia as follows. The Swain–Langley-positive phenotype and antigen previously referred to as Sl(a+) and Sla are now Sl:1 and Sl1, respectively; the allele Sla is now Sl 1. The antithetical phenotype and antigen previously referred to as Vil+ and Vil are now Sl:2 and Sl2, respectively; the allele Vil, is now Sl 2. Nomenclature for the Knops blood group, McCoy phenotype, antigen, and allele are McC(a+), McCa, McCa, and McC(b+), McCb, McCb (Geoff Daniels, personal communication).

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Zimmerman, P., Fitness, J., Moulds, J. et al. CR1 Knops blood group alleles are not associated with severe malaria in the Gambia. Genes Immun 4, 368–373 (2003). https://doi.org/10.1038/sj.gene.6363980

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