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Variability at the FCGR locus: characterization in Black South Africans and evidence for ethnic variation in and out of Africa

Genes & Immunity volume 17, pages 93–104 (2016)Cite this article

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Abstract

This study set out to comprehensively investigate all known functional FcγR variants in South African Black and Caucasian individuals. Population diversity was further assessed using data from the 1000 Genomes Project. In our cohort, Black South Africans neither possessed the haplotypes previously associated with increased surface densities of FcγRIIb and FcγRIIIa nor the FCGR2C haplotype recently associated with increased vaccine efficacy in the RV144 HIV-1 vaccine trial (despite 48.7% bearing the c.134-96T tag allele). Moreover, Africans (South Africans, Luhya Kenyans and Yoruba Nigerians) lack the FCGR2C c.798+1G splice-site allele required for the expression of functional FcγRIIc. Although the presence or absence of surface FcγRIIc did not affect natural killer cell-mediated antibody-dependent cellular cytotoxicity capability, this may be significant for other FcγRIIc-mediated functions. Overall, allele distribution and linkage disequilibrium in Africans and Caucasians differed in a manner that would suggest a differentially maintained balance of FcγR-mediated cell activation in these populations. Finally, significant variation observed among different African populations precludes the use of any one African population as a proxy for FcγR diversity in Africans. In conclusion, the findings of this study highlight further ethnic variation at the FCGR gene locus, in particular for FCGR2C, a gene with increasingly recognized clinical significance.

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Acknowledgements

The following reagents were obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: recombinant HIV-1BaL gp120 (Cat. no. 4961) from DAIDS, NIAID; HIV-1 gp120 Monoclonal Antibody (A32) (Cat. no. 11438) from Dr James E Robinson; and CEM.NKR from Dr Peter Cresswell. The anti-FcγRIIb/c clone 2B6 was a gift from MacroGenics. This work is based on the research supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa. Ria Lassaunière is the recipient of bursaries from the South African National Research Foundation, the Poliomyelitis Research Foundation and a University of the Witwatersrand postgraduate merit award.

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  1. Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa

    R Lassaunière & C T Tiemessen

  2. Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    R Lassaunière & C T Tiemessen

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  1. R Lassaunière
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Correspondence to C T Tiemessen.

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Lassaunière, R., Tiemessen, C. Variability at the FCGR locus: characterization in Black South Africans and evidence for ethnic variation in and out of Africa. Genes Immun 17, 93–104 (2016). https://doi.org/10.1038/gene.2015.60

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