Fc gamma receptor IIIB-NA gene frequencies in patients with systemic lupus erythematosus and healthy individuals of Malay and Chinese ethnicity

Yap, Siew Nee; Phipps, Maude E.; Manivasagar, M.; Bosco, John J.

doi:10.1016/s0165-2478(99)00061-9

Cited by 20 publications

(21 citation statements)

References 27 publications

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“…On the other hand, 12.5% of Caucasians and 17.8% of African-Americans genotyped exhibited the least favorable genotype combination. The reverse situation may apply among Japanese and Chinese subjects, among whom the H131 and NA1 alleles are predominant (18,48). The significance of the interplay between specific alleles of Fc␥RIIA and Fc␥RIIIB in defining susceptibility to other infectious or autoimmune diseases has not been established and awaits further investigation.…”

Section: Vol 7 2000mentioning

confidence: 99%

Evaluation of Human FcγRIIA (CD32) and FcγRIIIB (CD16) Polymorphisms in Caucasians and African-Americans Using Salivary DNA

Schie

Wilson²

2000

Clin Diagn Lab Immunol

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Two classes of low-affinity receptors for the Fc region of immunoglobulin G (IgG) (Fc␥R) are constitutively expressed on resting human neutrophils. These receptors, termed Fc␥RIIa (CD32) and Fc␥RIIIb (CD16), display biallelic polymorphisms which have functional consequences with respect to binding and/or ingestion of targets opsonized by human IgG subclass antibodies. The H131-R131 polymorphism of CD32 influences binding of human IgG2 and, to a lesser extent, human IgG3 to neutrophils. The neutrophil antigen (NA1-NA2) polymorphism of CD16 influences the efficiency of phagocytosis of bacteria opsonized by human IgG1 and IgG3. These polymorphisms may influence host susceptibility to certain infectious and/or autoimmune diseases, prompting interest in the development of facile methods for determination of CD32 and CD16 genotype in various clinical settings. We previously reported that genomic DNA from saliva is a suitable alternative to DNA from blood in PCR-based analyses of CD32 and CD16 polymorphisms. In the present study, we utilized for the first time this salivary DNA-based methodology to define CD32 and CD16 genotypes in 271 Caucasian and 118 African-American subjects and to investigate possible linkage disequilibrium between certain CD32 and CD16 genotypes in these two ethnic groups. H131 and R131 gene frequencies were 0.45 and 0.55, respectively, among Caucasians and 0.59 among African-Americans. NA1 and NA2 gene frequencies were 0.38 and 0.62 among Caucasians and 0.39 and 0.61 among African-Americans. Since Fc␥RIIa and Fc␥RIIIb synergize in triggering neutrophils, we also assessed the frequency of different CD32 and CD16 genotype combinations in these two groups. In both groups, the R/R131-NA2/NA2 genotype combination was more common than the H/H131-NA1/NA1 combination (threefold for Caucasians versus sevenfold for AfricanAmericans). Whether individuals with the combined R/R131-NA2/NA2 genotype are at greater risk for development of infectious and/or autoimmune diseases requires further investigation, which can be conveniently performed using DNA from saliva rather than blood.

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Section: Vol 7 2000mentioning

confidence: 99%

Evaluation of Human FcγRIIA (CD32) and FcγRIIIB (CD16) Polymorphisms in Caucasians and African-Americans Using Salivary DNA

Schie

Wilson²

2000

Clin Diagn Lab Immunol

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“…[16][17][18][19] Also there have been studies reporting the association of two common allotypes of FCGR3B with SLE. [20][21][22] However, the interpretation of these studies is bedevilled by the confounding effect of CNV of the FCGR3B gene.…”

Section: Introductionmentioning

confidence: 99%

Evidence for both copy number and allelic (NA1/NA2) risk at the FCGR3B locus in systemic lupus erythematosus

et al. 2010

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The Fcc-receptor locus on chromosome 1q23 shows copy-number variation (CNV), and it has previously been shown that individuals with reduced numbers of copies of the Fcc-receptor-IIIB gene (FCGR3B) have an increased risk of developing systemic lupus erythematosus (SLE). It is not understood whether the association arises from FCGR3B (CD16b) itself, is observed because of linkage disequilibrium with actual causal alleles and/or is an effect of CNV on flanking FCGR genes. Thus, we extended this previous work by genotyping the FCGR3B alleles NA1/NA2 and re-assaying CNV using a paralogue ratio test assay in a family study (365 families). We have developed a novel case/pseudo-control approach to analyse family data, as the phase of copy number (CN) is not known in parents and cannot always be inferred in offspring. The results, obtained by fitting logistic regression models, confirm the association of low CN of FCGR3B with SLE (P¼0.04). The risk conferred by low copies (o2) was contingent on FCGR3B allotype, being greater for deletion of NA1 than the for lower-affinity NA2. The simpler model with just CN was rejected in favour of the biallelic-CN model (P¼0.03). We observed a correlation (R 2 ¼0.75, Po0.0001) between FCGR3B CNV and neutrophil expression in both healthy controls and patients with SLE. Our results suggest that one mechanism by which CNV at this locus confers disease risk is directly as a result of reduced FccRIIIb function, either because of reduced expression (related to CNV) or because of reduced affinity for its ligand (NA1/NA2 allotype).

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“…In contrast, the FcγRIIA 131R allele was not increased in SLE or nephritis in African-Caribean, British, Dutch, Greek, Hispanic, Korean, and Spanish populations [127,130,134,139,[145][146][147][148][149]. Similarly, studies in Chinese, German, and African-American populations have found no associations between the FcγRIIIA 158F and the FcγRIIIB-NA2 allele [71,127,131,138,144,150,151].…”

Section: The Activating Fcrs In the Efferent Responsementioning

confidence: 89%

Activating and inhibitory FcγRs in autoimmune disorders

Nimmerjahn

2006

Springer Semin Immun

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Autoimmune disorders are characterized by the destruction of self-tissues by the immune system. Multiple checkpoints are in place to prevent autoreactivity under normal circumstances. Coexpression of activating and inhibitory Fc receptors (FcR) represents such a checkpoint by establishing a threshold for immune cell activation. In many human autoimmune diseases, however, balanced FcR expression is disturbed. Analysis of murine model systems provides strong evidence that aberrant FcR expression can result in uncontrolled immune responses and the initiation of autoimmune disease. This review will summarize this data and explain how this information might be used to better understand human autoimmune diseases and to develop novel therapeutic strategies.

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Fc gamma receptor IIIB-NA gene frequencies in patients with systemic lupus erythematosus and healthy individuals of Malay and Chinese ethnicity

Cited by 20 publications

References 27 publications

Evaluation of Human FcγRIIA (CD32) and FcγRIIIB (CD16) Polymorphisms in Caucasians and African-Americans Using Salivary DNA

Evaluation of Human FcγRIIA (CD32) and FcγRIIIB (CD16) Polymorphisms in Caucasians and African-Americans Using Salivary DNA

Evidence for both copy number and allelic (NA1/NA2) risk at the FCGR3B locus in systemic lupus erythematosus

Activating and inhibitory FcγRs in autoimmune disorders

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