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A complement receptor-1 polymorphism with high frequency in malaria endemic regions of Asia but not Africa

Genes & Immunity volume 6, pages 31–36 (2005)Cite this article

Abstract

Complement receptor-1 (CR1) is a ligand for rosette formation, a phenomenon associated with cerebral malaria (CM). Binding is dependent on erythrocyte CR1 copy number. In Caucasians, low CR1 expressors have two linked mutations. We determined the Q981H and HindIII RFLP distribution in differing population groups to ascertain a possible role in adaptive evolution. We examined 194 Caucasians, 180 Choctaw Indians, 93 Chinese-Taiwanese, 304 Cambodians, 89 Papua New Guineans (PNG) and 366 Africans. PCR/RFLP used HindIII for CR1 expression and BstNI for the Q981H mutation. DNA sequencing and pyrosequencing were performed to resolve inconclusive results. Gene frequencies for the L allele were 0.15 in Africans, 0.16 in Choctaws, 0.18 in Caucasians, 0.29 in Chinese-Taiwanese, 0.47 in Cambodians and 0.58 in PNG. Allelic frequency for 981H were 0.07 in Africans, 0.15 in Caucasians, 0.18 in Choctaws, 0.29 in Chinese-Taiwanese, 0.47 in Cambodians and 0.54 in PNG. The Q981H polymorphism correlates with the HindIII RFLP in most groups except West Africans and appears to be part of a low CR1 expression haplotype. The gene frequency for the haplotype is highest in the malaria-endemic areas of Asia, suggesting that this haplotype may have evolved because it protects from rosetting and CM.

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Acknowledgements

We thank Sue Riester of Somerset Laboratories, New York; Gwan Wu of the Shen Zhen Blood Center, Peoples Republic of China; Marie Lin of the Mackay Memorial Hospital, Taiwan; Frank Arnett and John Reveille of the University of Texas Medical School, Houston for providing materials from USA-Caucasians, Chinese, Taiwanese and Choctaw Indians, respectively. We are grateful to Chris Plowe of the University of Maryland Medical School, Ogobara Doumbo and Dapa Diallo of the University of Bamako who facilitated material collection from Mali. This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health grant RO1-AI-42367 (JMM) and Contract No. N01-AI-85346 (CVP). Additional funding was provided by the Somerset Laboratories, New York (JMM).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA

    B N Thomas & J M Moulds

  2. PPDH, EA 3309, IFR 53, URCA, Reims, France

    B Donvito & J H M Cohen

  3. ICAPB, University of Edinburgh, Ashworth Laboratories, Edinburgh, UK

    I Cockburn & J A Rowe

  4. Institut Pasteur du Cambodge (IPC), Monivong Bd, Phnom Penh, Cambodia

    T Fandeur

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  1. B N Thomas
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Correspondence to J M Moulds.

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Thomas, B., Donvito, B., Cockburn, I. et al. A complement receptor-1 polymorphism with high frequency in malaria endemic regions of Asia but not Africa. Genes Immun 6, 31–36 (2005). https://doi.org/10.1038/sj.gene.6364150

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