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.

journal_name

Immunogenetics

journal_title

Immunogenetics

authors

van der Pol WL,Jansen MD,Sluiter WJ,van de Sluis B,Leppers-van de Straat FG,Kobayashi T,Westendorp RG,Huizinga TW,van de Winkel JG

doi

10.1007/s00251-003-0574-9

subject

Has Abstract

pub_date

2003-07-01 00:00:00

pages

240-6

issue

4

eissn

0093-7711

issn

1432-1211

journal_volume

55

pub_type

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