Genetic diversity in human Fc receptor II for immunoglobulin G: Fc gamma receptor IIA ligand-binding polymorphism

Abstract

Fc gamma receptors, and in particular genetic variation in these receptors, are important in disorders of hose defense, immunohematologic disease, and systemic autoimmune diseases. We investigated the His-Arg (CAT/CGT) polymorphism at codon 131 of the Fc gamma receptor IIA gene, which influences ligand binding by the receptor. Previously, individuals had been classified phenotypically on the basis of differential binding of murine immunoglobulin G1, but the Fc gamma receptor IIA genotype distribution has not been reported. We used selective PCR-based sequence analysis of genomic DNA to determine the distribution in healthy individuals. For African-Americans, the genotype distribution was determined to be A/A (14%), A/G (60%), and G/G (26%); for Caucasian Americans, the distribution was A/A (30%), A/G (51%), and G/G (19%). These data correlate well with phenotypic data. We implemented a nonradioactive single-stranded conformational polymorphism analysis to rapidly identify all three genotypes. The PCR-single-stranded conformational polymorphism analysis method will facilitate studies of the genotype distribution in individuals with disorders of immune function.

The FCGR2A— Arg131 variant is no major mortality factor in the elderly — evidence from a German centenarian study

“…The His131Arg polymorphism was found to be in Hardy–Weinberg equilibrium in all three samples ( P > 0.05). The observed frequencies are well within the range reported previously for Caucasians (Bredius et al ., 1994; Reilly et al ., 1995). A power calculation revealed that given our sample sizes and an average 131Arg allele frequency of 0.46, we would be able to detect a factor with a comparatively low relative risk of 1.47 (at a significance level of 0.05 and a power of 80%).…”

Analysis of Fc gamma receptor II (CD32) polymorphism in populations of African and South Asian ancestry reveals east–west geographic gradients of allele frequencies

“…We then compared the FcγR allele profiles in our groups with the profiles of a number of previously analysed populations (Reilly et al ., 1994; Botto et al ., 1996; Salmon et al ., 1996; Lehrnbecher et al ., 1999; van Schie & Wilson, 2000; Van den Berg et al ., 2001). There were no significant differences (data not shown) between the frequencies of the FcγRIIA alleles in Trinidadian Africans and those observed in African‐Caribbeans from the UK (Botto et al ., 1996), African‐Americans from the USA (Reilly et al ., 1994; Salmon et al ., 1996; Lehrnbecher et al ., 1999; van Schie & Wilson, 2000) or Ethiopians from East Africa (van den Berg et al ., 2001).…”

Fc Receptors in Immune Responses

“…The role of human FcR in experimental autoimmune diseases has been investigated in transgenic mice. Human FcgRIIA induced ITP (Reilly et al, 1994) or arthritis (Pietersz et al, 2009). The expression of human FcgRI in mice lacking activating FcR restored arthritis symptoms (Mancardi et al, submitted).…”