Variant genotypes of the low-affinity Fcγ receptors in two control populations and a review of low-affinity Fcγ receptor polymorphisms in control and disease populations

Fc gamma-receptors (Fc gamma R) provide a critical link between humoral and cellular immunity. The genes of the low-affinity receptors for IgG and their isoforms, namely, Fc gamma RIIa, Fc gamma RIIb, Fc gamma RIIIa, Fc gamma RIIIb, and SH-Fc gamma RIIIb, are located in close proximity on chromosome 1q22. Variant alleles may differ in biologic activity and a number of studies have reported the frequencies of variant Fc gamma R alleles in both disease and control populations. No large study has evaluated the possibility of a nonrandom distribution of variant genotypes. We analyzed 395 normal individuals (172 African Americans [AA] and 223 Caucasians [CA]) at the following loci: Fc gamma RIIa, Fc gamma RIIIa, and Fc gamma RIIIb, including the SH-Fc gamma RIIIb. The genotypic distributions of Fc gamma RIIa, Fc gamma RIIIa, and Fc gamma RIIIb conform to the Hardy-Weinberg law in each group. There was no strong evidence that combinations of 2-locus genotypes of the 3 loci deviated from random distributions in these healthy control populations. The distribution of SH-Fc gamma RIIIb is underrepresented in CA compared with AA (P < .0001) controls. A previously reported variant Fc gamma RIIb was not detected in 70 normal individuals, indicating that this allele, if it exists, is very rare (<1%). In conclusion, we present data that should serve as the foundation for the interpretation of association studies involving multiple variant alleles of the low-affinity Fc gamma R. (C) 1999 by The American Society of Hematology.