title: Evidence for non-random distribution of Fcgamma receptor genotype combinations.
abstract: Human IgG receptors (FcgammaR) display considerable heterogeneity, and are crucial immune response modulating molecules. FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB display functional biallelic polymorphisms. FcgammaR polymorphisms have been found associated with susceptibility to infectious and autoimmune diseases. Linked transmission of FcgammaR alleles was studied by determining the distribution of FcgammaRIIA-FcgammaRIIIA-FcgammaRIIIB genotype combinations in 514 Dutch Caucasian, and 149 Japanese blood donors. The structure of the FcgammaR locus was studied by radiation hybrid mapping of FcgammaRIA, FcgammaRIIA, FcgammaRIIB, FcgammaRIIIA, FcgammaRIIIB, and adjacent genes from the pentraxin family. In addition, crossing-over frequencies within the FcgammaR locus were determined in 63 Dutch Caucasian families, encompassing 183 individuals. FcgammaRII and FcgammaRIII subclasses were mapped in close proximity (0.47-3.14 cR). Accordingly, crossing-over frequencies within the FcgammaRII-III locus in Dutch families were low. Analysis of combined FcgammaR genotypes strongly suggested non-random distribution of FcgammaRIIA-FcgammaRIIIA-, and FcgammaRIIIA-FcgammaRIIIB genotypes in Dutch donors (P<0.001 and P<0.00001, respectively), and of FcgammaRIIA-FcgammaRIIIb genotypes in Japanese blood donors (P<0.02). Frequencies of FcgammaRII-FcgammaRIII haplotypes differed significantly between Dutch and Japanese (P<0.00001). This study provides important information for the interpretation of studies reporting associations of FcgammaR alleles with disease, and underscores the apparent differences in FcgammaR heterogeneity between ethnic groups.
authors.affiliation: Department of Immunology, Laboratory for Immunotherapy, KC.02-085.2, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands. L.vdPol@lab.azu.nl
authors.forename: W-Ludo
authors.initials: WL
authors.lastname: van der Pol
authors.forename: Marc D
authors.initials: MD
authors.lastname: Jansen
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Sluiter
authors.forename: Bart
authors.initials: B
authors.lastname: van de Sluis
authors.forename: Fredriek G J
authors.initials: FG
authors.lastname: Leppers-van de Straat
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Jan G J
authors.initials: JG
authors.lastname: van de Winkel
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D009426:Netherlands; D011110:Polymorphism, Genetic; D021101:Radiation Hybrid Mapping; D017452:Receptors, IgG / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D017452:Receptors, IgG