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Evidence for non-random distribution of Fcγ receptor genotype combinations

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Abstract

Human IgG receptors (FcγR) display considerable heterogeneity, and are crucial immune response modulating molecules. FcγRIIA, FcγRIIIA, and FcγRIIIB display functional biallelic polymorphisms. FcγR polymorphisms have been found associated with susceptibility to infectious and autoimmune diseases. Linked transmission of FcγR alleles was studied by determining the distribution of FcγRIIA-FcγRIIIA-FcγRIIIB genotype combinations in 514 Dutch Caucasian, and 149 Japanese blood donors. The structure of the FcγR locus was studied by radiation hybrid mapping of FcγRIA, FcγRIIA, FcγRIIB, FcγRIIIA, FcγRIIIB, and adjacent genes from the pentraxin family. In addition, crossing-over frequencies within the FcγR locus were determined in 63 Dutch Caucasian families, encompassing 183 individuals. FcγRII and FcγRIII subclasses were mapped in close proximity (0.47–3.14 cR). Accordingly, crossing-over frequencies within the FcγRII-III locus in Dutch families were low. Analysis of combined FcγR genotypes strongly suggested non-random distribution of FcγRIIA-FcγRIIIA-, and FcγRIIIA-FcγRIIIB genotypes in Dutch donors (P<0.001 and P<0.00001, respectively), and of FcγRIIA-FcγRIIIb genotypes in Japanese blood donors (P<0.02). Frequencies of FcγRII-FcγRIII haplotypes differed significantly between Dutch and Japanese (P<0.00001). This study provides important information for the interpretation of studies reporting associations of FcγR alleles with disease, and underscores the apparent differences in FcγR heterogeneity between ethnic groups.

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Acknowledgements

We thank N. Westerdaal and V. Keijsers for excellent technical assistance, and Dr. C. Wijmenga for help with radiation hybrid mapping and valuable comments on the manuscript. This work was supported by a grant from the Netherlands Organization for Scientific Research (NWO grant no. 95-10-624).

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Authors and Affiliations

  1. Department of Immunology, Laboratory for Immunotherapy, KC.02-085.2, University Medical Center Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands

    W.-Ludo van der Pol, Marc D. Jansen, Fredriek G. J. Leppers-van de Straat & Jan G. J. van de Winkel

  2. Department of Internal Medicine, University Hospital Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    Wim J. Sluiter

  3. Department of Medical Genetics, University Medical Center Utrecht, Lundlaan 6, 3584 EA, EA Utrecht, The Netherlands

    Bart van de Sluis

  4. Department of Periodontology, Niigata University School of Dentistry, Gakko-cho 2-5274, Niigata, Japan

    Tetsuo Kobayashi

  5. Departments of General Internal Medicine and Rheumatology, University Medical Center Leiden, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands

    Rudi G. J. Westendorp & Tom W. J. Huizinga

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  1. W.-Ludo van der Pol
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  2. Marc D. Jansen
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Correspondence to W.-Ludo van der Pol.

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van der Pol, WL., Jansen, M.D., Sluiter, W.J. et al. Evidence for non-random distribution of Fcγ receptor genotype combinations. Immunogenetics 55, 240–246 (2003). https://doi.org/10.1007/s00251-003-0574-9

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  • DOI: https://doi.org/10.1007/s00251-003-0574-9

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