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Blood, Vol. 94 No. 12 (December 15), 1999:
pp. 4220-4232
Variant Genotypes of the Low-Affinity Fc Receptors in Two Control
Populations and a Review of Low-Affinity Fc Receptor Polymorphisms
in Control and Disease Populations
Thomas Lehrnbecher,
Charles B. Foster,
Shaoxian Zhu,
Susan F. Leitman,
Lynn R. Goldin,
Konrad Huppi, and
Stephen J. Chanock
From the Immunocompromised Host Section, Pediatric Oncology Branch,
the Genetic Epidemiology Branch, Division of Cancer Epidemiology and
Genetics, and the Laboratory of Genetics, National Cancer Institute,
and the Department of Transfusion Medicine, Clinical Center, National
Institutes of Health, Bethesda, MD.
Fc -receptors (FcR) provide a critical link between humoral and
cellular immunity. The genes of the low-affinity receptors for IgG and
their isoforms, namely, FcRIIa, FcRIIb, FcRIIIa, FcRIIIb,
and SH-FcRIIIb, 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 FcR 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: FcRIIa, FcRIIIa, and FcRIIIb,
including the SH-FcRIIIb. The genotypic distributions of FcRIIa,
FcRIIIa, and FcRIIIb 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-FcRIIIb is
underrepresented in CA compared with AA (P < .0001) controls. A previously reported variant FcRIIb 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 FcR.
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