Variant genotypes of the low-affinity Fcgamma receptors in two control populations and a review of low-affinity Fcgamma receptor polymorphisms in control and disease populations.
Fcgamma-receptors (FcgammaR) provide a critical link between humoral and cellular immunity. The genes of the low-affinity receptors for IgG and their isoforms, namely, FcgammaRIIa, FcgammaRIIb, FcgammaRIIIa, FcgammaRIIIb, and SH-FcgammaRIIIb, 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 FcgammaR 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: FcgammaRIIa, FcgammaRIIIa, and FcgammaRIIIb, including the SH-FcgammaRIIIb. The genotypic distributions of FcgammaRIIa, FcgammaRIIIa, and FcgammaRIIIb 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-FcgammaRIIIb is underrepresented in CA compared with AA (P < .0001) controls. A previously reported variant FcgammaRIIb 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 FcgammaR.
Lehrnbecher
T
T
Immunocompromised Host Section, Pediatric Oncology Branch, Division of Cancer Epidemiology, National Cancer Institute, Bethesda, MD 20892, USA.
Foster
C B
CB
Zhu
S
S
Leitman
S F
SF
Goldin
L R
LR
Huppi
K
K
Chanock
S J
SJ
D000483:Alleles; D044383:Black People; D005787:Gene Frequency; D015894:Genome, Human; D006801:Humans; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D044465:White People; D001741:Black or African American
D017452:Receptors, IgG