Home LiteratureArticle Details
PMID: 12830330 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Evidence for non-random distribution of Fcgamma receptor genotype combinations.

Immunogenetics ·Vol. 55 ·No. 4 ·2003-07-00 ·Pages 240-6

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

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.

MeSH Terms
Alleles Asians/genetics Gene Frequency Genotype Haplotypes Humans Japan Netherlands Polymorphism, Genetic Radiation Hybrid Mapping Receptors, IgG/genetics Whites/genetics
Chemicals
Receptors, IgG
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
van der Pol W-Ludo
Department of Immunology, Laboratory for Immunotherapy, KC.02-085.2, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands. L.vdPol@lab.azu.nl
Jansen Marc D
Sluiter Wim J
van de Sluis Bart
Leppers-van de Straat Fredriek G J
Kobayashi Tetsuo
Westendorp Rudi G J
Huizinga Tom W J
van de Winkel Jan G J
References (54)
54 references, click to expand
  1. Impaired IgG-dependent anaphylaxis and Arthus reaction in Fc gamma RIII (CD16) deficient mice.
    Immunity. 1996 Aug;5(2):181-8 PMID: 8769481
  2. Augmented humoral and anaphylactic responses in Fc gamma RII-deficient mice.
    Nature. 1996 Jan 25;379(6563):346-9 PMID: 8552190
  3. Linkage disequilibria between Duffy blood groups, Fc gamma IIa and Fc gamma IIIb allotypes.
    Exp Clin Immunogenet. 1997;14(4):235-42 PMID: 9523159
  4. Heparin-induced thrombocytopenia: new insights into the impact of the FcgammaRIIa-R-H131 polymorphism.
    Blood. 1998 Sep 1;92(5):1526-31 PMID: 9716579
  5. Role of the Fcgamma receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: a meta-analysis.
    Arthritis Rheum. 2002 Jun;46(6):1563-71 PMID: 12115187
  6. Fc receptors are required in passive and active immunity to melanoma.
    Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):652-6 PMID: 9435247
  7. Neutrophil Fc gamma RIIIb deficiency, nature, and clinical consequences: a study of 21 individuals from 14 families.
    Blood. 1995 Sep 15;86(6):2403-13 PMID: 7662988
  8. Immune cell signaling defects in lupus: activation, anergy and death.
    Immunol Today. 1999 Mar;20(3):119-24 PMID: 10203702
  9. Organization of the human and mouse low-affinity Fc gamma R genes: duplication and recombination.
    Science. 1990 May 11;248(4956):732-5 PMID: 2139735
  10. On the interaction of IgG subclasses with the low affinity Fc gamma RIIa (CD32) on human monocytes, neutrophils, and platelets. Analysis of a functional polymorphism to human IgG2.
    J Clin Invest. 1992 Oct;90(4):1537-46 PMID: 1401085
  11. Myelin protein zero gene mutated in Charcot-Marie-tooth type 1B patients.
    Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10856-60 PMID: 7504284
  12. Assignment of three human high-affinity Fc gamma receptor I genes to chromosome 1, band q21.1.
    Immunogenetics. 1993;38(1):57-9 PMID: 8462996
  13. Inhibitory pathways triggered by ITIM-containing receptors.
    Adv Immunol. 1999;72:149-77 PMID: 10361574
  14. Microsatellite alleles and single nucleotide polymorphisms (SNP) combine to form four major haplotype families at the human interleukin-10 (IL-10) locus.
    Genes Immun. 1999 Nov;1(2):151-5 PMID: 11196662
  15. Fine mapping of the human pentraxin gene region on chromosome 1q23.
    Immunogenetics. 1996;44(1):62-9 PMID: 8613143
  16. A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease.
    J Clin Invest. 1997 Sep 1;100(5):1059-70 PMID: 9276722
  17. Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility.
    Arthritis Rheum. 2002 May;46(5):1242-54 PMID: 12115230
  18. Fc gamma RIIIB gene duplication: evidence for presence and expression of three distinct Fc gamma RIIIB genes in NA(1+,2+)SH(+) individuals.
    Blood. 1998 Jan 15;91(2):673-9 PMID: 9427724
  19. Association of Fc gamma receptor IIIB, but not of Fc gamma receptor IIA and IIIA polymorphisms with systemic lupus erythematosus in Japanese.
    Genes Immun. 1999 Sep;1(1):53-60 PMID: 11197306
  20. Role of neutrophil Fc gamma RIIa (CD32) and Fc gamma RIIIb (CD16) polymorphic forms in phagocytosis of human IgG1- and IgG3-opsonized bacteria and erythrocytes.
    Immunology. 1994 Dec;83(4):624-30 PMID: 7875742
  21. Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions.
    J Exp Med. 1989 Aug 1;170(2):481-97 PMID: 2526846
  22. Biallelic neutrophil Na-antigen system is associated with a polymorphism on the phospho-inositol-linked Fc gamma receptor III (CD16).
    Blood. 1990 Jan 1;75(1):213-7 PMID: 2136803
  23. Genomic organization of classical human low-affinity Fcgamma receptor genes.
    Genes Immun. 2002 Oct;3 Suppl 1:S51-6 PMID: 12215903
  24. A novel PCR-based method for direct Fc gamma receptor IIIa (CD16) allotyping.
    J Immunol Methods. 2000 Aug 28;242(1-2):127-32 PMID: 10986395
  25. Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype.
    Blood. 1997 Aug 1;90(3):1109-14 PMID: 9242542
  26. Neutrophil antigen (FcgammaRIIIB) SH gene frequencies in six racial groups.
    Blood. 1999 Feb 1;93(3):1115-6 PMID: 10025985
  27. Ethnic variation in frequency of an allelic polymorphism of human Fc gamma RIIA determined with allele specific oligonucleotide probes.
    J Immunol Methods. 1994 Aug 1;173(2):207-17 PMID: 8046255
  28. Fcgamma receptor polymorphisms in Wegener's granulomatosis: risk factors for disease relapse.
    Arthritis Rheum. 1999 Sep;42(9):1823-7 PMID: 10513795
  29. Genetic influence on cytokine production and fatal meningococcal disease.
    Lancet. 1997 Jan 18;349(9046):170-3 PMID: 9111542
  30. Role for a glycan phosphoinositol anchor in Fc gamma receptor synergy.
    J Cell Biol. 1997 Dec 1;139(5):1209-17 PMID: 9382867
  31. Human Fc gamma RIII: cloning, expression, and identification of the chromosomal locus of two Fc receptors for IgG.
    Proc Natl Acad Sci U S A. 1989 Feb;86(3):1013-7 PMID: 2521732
  32. Heterotypic Fc gamma R clusters evoke a synergistic Ca2+ response in human neutrophils.
    J Biol Chem. 1995 May 5;270(18):10671-9 PMID: 7738004
  33. A single amino acid in the second Ig-like domain of the human Fc gamma receptor II is critical for human IgG2 binding.
    J Immunol. 1991 Aug 15;147(4):1338-43 PMID: 1831223
  34. Differential regulation of human neutrophil FcgammaRIIa (CD32) and FcgammaRIIIb (CD16)-induced Ca2+ transients.
    J Biol Chem. 1998 Apr 3;273(14):8071-9 PMID: 9525908
  35. Gain-of-function mutations in FcgammaRI of NOD mice: implications for the evolution of the Ig superfamily.
    EMBO J. 1998 Jul 15;17(14):3850-7 PMID: 9670002
  36. Genetic linkage and association of Fcgamma receptor IIIA (CD16A) on chromosome 1q23 with human systemic lupus erythematosus.
    Arthritis Rheum. 2002 Aug;46(8):2132-40 PMID: 12209518
  37. Modulation of immune complex-induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc receptors.
    J Exp Med. 1999 Jan 4;189(1):179-85 PMID: 9874574
  38. Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications.
    Immunol Today. 1993 May;14(5):215-21 PMID: 8517920
  39. Molecular basis for a polymorphism of human Fc gamma receptor II (CD32).
    J Exp Med. 1990 Jul 1;172(1):19-25 PMID: 2141627
  40. Allelic polymorphisms of human Fc gamma receptor IIA and Fc gamma receptor IIIB. Independent mechanisms for differences in human phagocyte function.
    J Clin Invest. 1992 Apr;89(4):1274-81 PMID: 1532589
  41. 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.
    Blood. 1999 Dec 15;94(12):4220-32 PMID: 10590067
  42. Antibody-mediated modulation of Cryptococcus neoformans infection is dependent on distinct Fc receptor functions and IgG subclasses.
    J Exp Med. 1998 Feb 16;187(4):641-8 PMID: 9463414
  43. Cytotoxic antibodies trigger inflammation through Fc receptors.
    Immunity. 1995 Jul;3(1):21-6 PMID: 7621075
  44. Seven single nucleotide substitutions in human Fc(gamma) receptor IIB gene.
    Tissue Antigens. 2001 Nov;58(5):339-42 PMID: 11844146
  45. The human low affinity immunoglobulin G Fc receptor IIC gene is a result of an unequal crossover event.
    J Biol Chem. 1993 Apr 5;268(10):7346-9 PMID: 8463268
  46. Polymorphism of IgG Fc receptors in meningococcal disease.
    Ann Intern Med. 1993 Oct 1;119(7 Pt 1):636 PMID: 8363182
  47. Relevance of Fcgamma receptor and interleukin-10 polymorphisms for meningococcal disease.
    J Infect Dis. 2001 Dec 15;184(12):1548-55 PMID: 11740730
  48. Characterization of a new alloantigen (SH) on the human neutrophil Fc gamma receptor IIIb.
    Blood. 1997 Feb 1;89(3):1027-34 PMID: 9028335
  49. IgG receptor polymorphisms: risk factors for disease.
    Immunogenetics. 1998 Aug;48(3):222-32 PMID: 9683667
  50. Frequency of the polymorphonuclear neutrophil Fc gamma receptor III deficiency in the French population and its involvement in the development of neonatal alloimmune neutropenia.
    Blood. 1992 Apr 15;79(8):2131-4 PMID: 1532916
  51. Fc receptors initiate the Arthus reaction: redefining the inflammatory cascade.
    Science. 1994 Aug 19;265(5175):1095-8 PMID: 8066448
  52. Crystal structure of the human leukocyte Fc receptor, Fc gammaRIIa.
    Nat Struct Biol. 1999 May;6(5):437-42 PMID: 10331870
  53. Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis.
    Science. 1998 Feb 13;279(5353):1052-4 PMID: 9461440
  54. Ethnic differences in the lymphocyte proliferative response induced by a murine IgG1 antibody, Leu-4, to the T3 molecule.
    J Exp Med. 1984 Jul 1;160(1):303-9 PMID: 6429266
Article Info
Journal
Immunogenetics
Abbr.
Immunogenetics
ISSN
0093-7711
DOI
10.1007/s00251-003-0574-9
Email
l.vdpol@lab.azu.nl
Published
2003-07-00
Epub
2003-00-26
Pages
240-6
Language
English
Region
United States
NLM ID
0420404
Subset
IM
External Links
PubMed source DOI: 10.1007/s00251-003-0574-9 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2