Evidence for non-random distribution of Fcγ receptor genotype combinations

Human IgG receptors (Fc gamma R) display considerable heterogeneity, and are crucial immune response modulating molecules.Fc gamma RIIA,Fc gamma RIIIA, andFc gamma RIIIB display functional biallelic polymorphisms.Fc gamma R polymorphisms have been found associated with susceptibility to infectious and autoimmune diseases. Linked transmission ofFc gamma R alleles was studied by determining the distribution ofFc gamma RIIA-Fc gamma RIIIA-Fc gamma RIIIB genotype combinations in 514 Dutch Caucasian, and 149 Japanese blood donors. The structure of theFc gamma R locus was studied by radiation hybrid mapping ofFc gamma RIA,Fc gamma RIIA,Fc gamma RIIB,Fc gamma RIIIA,Fc gamma RIIIB , and adjacent genes from the pentraxin family. In addition, crossing-over frequencies within theFc gamma R locus were determined in 63 Dutch Caucasian families, encompassing 183 individuals.Fc gamma RII andFc gamma RIII subclasses were mapped in close proximity (0.47-3.14 cR). Accordingly, crossing-over frequencies within theFc gamma RII-III locus in Dutch families were low. Analysis of combinedFc gamma R genotypes strongly suggested non-random distribution ofFc gamma RIIA-Fc gamma RIIIA-, andFc gamma RIIIA-Fc gamma RIIIB genotypes in Dutch donors (P