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 P FcγRIIA-FcγRIIIb genotypes in Japanese blood donors (P FcγRII-FcγRIII haplotypes differed significantly between Dutch and Japanese (P FcγR alleles with disease, and underscores the apparent differences in FcγR heterogeneity between ethnic groups.