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Evidence for malaria selection of a CR1 haplotype in Sardinia

Genes & Immunity volume 12, pages 582–588 (2011)Cite this article

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Abstract

Complement receptor 1 (CR1) levels have been associated with malarial susceptibility and/or severity of the disease in different population groups, and CR1 is a receptor for Plasmodium falciparum. In this study, multiple CR1 single-nucleotide polymorphisms (SNPs) showed strong evidence of population differentiation between Sardinian and other European ethnic groups. Cross population algorithms comparing haplotype structure and differences in haplotype and allele frequency distribution provided additional support for natural selection of CR1 in Sardinia. The predominant Sardinian CR1 haplotype included SNPs that are associated with decreased CR1 levels in Europeans and other population groups. Previous studies have shown that the SNPs within the dominant Sardinian haplotype have a significantly higher frequency in a malaria endemic compared with non-endemic regions in India. Together with the historical evidence of the prevalence of malaria in Sardinia, these data support the role of malaria leading to positive selection of this CR1 haplotype in Sardinia.

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Acknowledgements

This study was in part supported by the US National Institutes of Health (R01 DK056839, and a grant to HYPERGENES (European Network for Genetic-Epidemiological Studies HEALTH-F4-2007-201550.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Medicine, Rowe Program in Human Genetics, University of California, Davis, CA, USA

    R Kosoy, M Ransom & M F Seldin

  2. Department of Genetics, Harvard Medical School, Boston, MA, USA

    H Chen

  3. Centro Trasfusionale e di Immunoematologia, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy

    M Marconi

  4. Università degli Studi di Milano, Milan, Italy

    F Macciardi & D Cusi

  5. Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA

    F Macciardi

  6. Hypertension and Related Diseases Centre, Chair of Emergency Medicine, Università di Sassari, Sassari, Italy

    N Glorioso

  7. Feinstein Institute for Medical Research, North Shore LIJ Health System, Manhasset, NY, USA

    P K Gregersen

  8. Genomics and Bioinformatics Unit, Fondazione Filarete, Milan, Italy

    D Cusi

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  1. R Kosoy
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Correspondence to M F Seldin.

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Kosoy, R., Ransom, M., Chen, H. et al. Evidence for malaria selection of a CR1 haplotype in Sardinia. Genes Immun 12, 582–588 (2011). https://doi.org/10.1038/gene.2011.33

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