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Gwan Gyu Song - One of the best experts on this subject based on the ideXlab platform.
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Association between FCGR3B copy number variations and susceptibility to autoimmune diseases: a meta-analysis
Inflammation Research, 2015Co-Authors: Sung Jae Choi, Jong Dae Ji, Gwan Gyu SongAbstract:Objective This study determined whether FCGR3B copy number variations (CNVs) were associated with susceptibility to autoimmune diseases. Methods A meta-analysis was conducted to determine the association between FCGR3B CNVs and susceptibility to autoimmune diseases by comparing low FCGR3B CN (2 to ≤2). Results In all, 28 comparative studies from 15 reports involving 12,160 patients and 11,103 controls were included in this meta-analysis. The meta-analysis showed a significant association between low FCGR3B CN and autoimmune diseases (OR = 1.496, 95 % CI = 1.301–1.716, p = 1.0 × 10^−9). Subgroup analysis according to ethnicity indicated an association between low FCGR3B CN and autoimmune diseases in Caucasians (OR = 1.482, 95 % CI = 1.219–1.801, p = 7.7 × 10^−6) and Asians (OR = 1.498, 95 % CI = 1.306–1.717, p = 1.0 × 10^−9). Meta-analysis according to the type of autoimmune disease indicated a significant association of low FCGR3B CN with systemic lupus erythematosus (SLE; OR = 1.797, 95 % CI = 1.562–2.068, p
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association between FCGR3B copy number variations and susceptibility to autoimmune diseases a meta analysis
Inflammation Research, 2015Co-Authors: Sung Jae Choi, Jong Dae Ji, Gwan Gyu SongAbstract:Objective This study determined whether FCGR3B copy number variations (CNVs) were associated with susceptibility to autoimmune diseases.
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fcgr2a fcgr3a FCGR3B polymorphisms and susceptibility to rheumatoid arthritis a meta analysis
Clinical and Experimental Rheumatology, 2015Co-Authors: Gwan Gyu SongAbstract:Abstract The aim of this study is to explore whether Fc gamma receptor (FCGR) polymorphisms are associated with the susceptibility to rheumatoid arthritis (RA). We conducted a meta-analysis on the association between FCGR2A H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms and RA susceptibility. A total of seventeen studies reported in fourteen articles (4,418 patients with RA and 3,560 controls) were considered in our meta-analysis. In all of the study subjects, meta-analysis indicated an association between RA and FCGR2A R allele (OR=0.877, 95% CI=0.792-0.971, p=0.011). Stratification by ethnicity indicated an association between FCGR2A R allele and RA in Europeans (OR=0.816, 95% CI=0.687-0.968, p=0.020), but not in East Asians (OR=0.900, 95% CI=0.778-1.040, p=0.154). Meta-analysis revealed an association between RA and FCGR3A VV vs. FF genotype in all the study subjects (OR=1.210, 95% CI=1.067-1.479, p=0.006). Stratification by ethnicity indicated an association between FCGR3A VV genotype and RA compared toFF genotype in Europeans (OR=1.350, 95% CI=1.107-1.646, p=0.003), but not in East Asians and South Asians. No association was observed between RA and FCGR3B polymorphisms on performing the meta-analysis. Although no relationship was found between the FCGR3B polymorphism and RA susceptibility, FCGR2A and FCGR3A polymorphisms were found to be associated with RA in Europeans, but not in Asians.
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associations between fcgr2a rs1801274 fcgr3a rs396991 FCGR3B na1 na2 polymorphisms and periodontitis a meta analysis
Molecular Biology Reports, 2013Co-Authors: Gwan Gyu SongAbstract:The aim of this study was to determine whether the Fcγ receptors (FCGRs) polymorphisms confer susceptibility to periodontitis in ethnically different populations. We did a literature search using PubMed and Embase, and conducted a meta-analysis on the associations between the FCGR2A H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms and periodontitis using allele contrast, the recessive model, the dominant model, and the homozygote contrast. A total of 17 separate comparisons with 1,421 patients with periodontitis and 1,454 controls, involving six Caucasian, six East Asian, two African and one South Asian population were considered in the meta-analysis. Meta-analysis of the FCGR2A H131R polymorphism showed no association between periodontitis and the FCGR2A R allele (OR = 0.987, 95 % CI = 0.881–1.107, p = 0.827). Stratification by ethnicity revealed an association between the RR+RH genotype with periodontitis in Caucasian population (OR = 0.624, 95 % CI = 0.479–0.813, p = 4.7 × 10−5), but not in East Asian, and African populations. Meta-analysis of the FCGR3A F158V polymorphism revealed an association between the FCGR3A V allele and periodontitis is in Caucasians (OR = 1.457, 95 % CI = 1.014–2.092, p = 0.042), but not in East Asians and Africans. In addition, analysis using the dominant model and homozygote contrast showed the same pattern for the FCGR3A V allele. Meta-analysis of the FCGR3B NA1/NA2 polymorphism using the recessive model revealed a significant association between the NA2/NA2 genotype and periodontitis in aggressive periodontitis (OR = 2.853, 95 % CI = 1.673–4.863, 1.1 × 10−5). This meta-analysis demonstrates that the FCGR2A, and FCGR3A polymorphisms may confer susceptibility to periodontitis in Caucasians, and that the FCGR3B polymorphism may be associated with susceptibility to aggressive periodontitis.
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Associations between FCGR2A rs1801274, FCGR3A rs396991, FCGR3B NA1/NA2 polymorphisms and periodontitis: a meta-analysis
Molecular Biology Reports, 2013Co-Authors: Gwan Gyu SongAbstract:The aim of this study was to determine whether the Fcγ receptors (FCGRs) polymorphisms confer susceptibility to periodontitis in ethnically different populations. We did a literature search using PubMed and Embase, and conducted a meta-analysis on the associations between the FCGR2A H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms and periodontitis using allele contrast, the recessive model, the dominant model, and the homozygote contrast. A total of 17 separate comparisons with 1,421 patients with periodontitis and 1,454 controls, involving six Caucasian, six East Asian, two African and one South Asian population were considered in the meta-analysis. Meta-analysis of the FCGR2A H131R polymorphism showed no association between periodontitis and the FCGR2A R allele (OR = 0.987, 95 % CI = 0.881–1.107, p = 0.827). Stratification by ethnicity revealed an association between the RR+RH genotype with periodontitis in Caucasian population (OR = 0.624, 95 % CI = 0.479–0.813, p = 4.7 × 10−5), but not in East Asian, and African populations. Meta-analysis of the FCGR3A F158V polymorphism revealed an association between the FCGR3A V allele and periodontitis is in Caucasians (OR = 1.457, 95 % CI = 1.014–2.092, p = 0.042), but not in East Asians and Africans. In addition, analysis using the dominant model and homozygote contrast showed the same pattern for the FCGR3A V allele. Meta-analysis of the FCGR3B NA1/NA2 polymorphism using the recessive model revealed a significant association between the NA2/NA2 genotype and periodontitis in aggressive periodontitis (OR = 2.853, 95 % CI = 1.673–4.863, 1.1 × 10−5). This meta-analysis demonstrates that the FCGR2A, and FCGR3A polymorphisms may confer susceptibility to periodontitis in Caucasians, and that the FCGR3B polymorphism may be associated with susceptibility to aggressive periodontitis.
Maureen Rischmueller - One of the best experts on this subject based on the ideXlab platform.
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No Association between FCγR3B Copy Number Variation and Susceptibility to Biopsy-Proven Giant Cell Arteritis
Arthritis, 2013Co-Authors: E. Dunstan, Maureen Rischmueller, Susan Lester, Rachel J. Black, Helen H.l. Chan, Alex W. Hewitt, Catherine L HillAbstract:Objective. To determine the relationship between FCGR3B gene copy number variation (CNV) and biopsy proven giant cell arteritis (GCA). Methods. FCGR3B CNV was determined in 139 Australian biopsy proven GCA patients and 162 population matched controls, using a duplex qPCR assay and RNase P as the reference gene. Copy number was determined using Copy Caller software (v.1.0, Applied Biosystems, USA). CNV genotypes were classified into 3 groups (
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susceptibility for lupus nephritis by low copy number of the FCGR3B gene is linked to increased levels of pathogenic autoantibodies
Autoimmune Diseases, 2013Co-Authors: Johannes C Nossent, Andrea Beckermerok, Maureen Rischmueller, Susan LesterAbstract:Low copy number (CN) of the FCGR3B gene reduces FCGR3B membrane expression on neutrophils and results in clearance of a smaller amount of immune complex. We investigated FCGR3B CN in relation to the clinical phenotype in a Caucasian SLE cohort (n = 107). FCGR3B CN was determined by three different qPCR parameter estimations (Ct−, Cy0, and cpD1) and confirmed by the FCGR2C/FCGR2A paralog ratio test. Clinical and serological data were then analyzed for their association with FCGR3B CN. Low FCGR3B CN ( 2). In multivariate analyses, LN was independently associated with anti-C1q-Ab levels (P = 0.03) and low FCGR3B CN (P = 0.09). We conclude that the susceptibility for LN in patients with low FCGR3B CN is linked to increased levels of pathogenic autoantibodies.
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low copy number of the fc γ receptor 3b gene FCGR3B is a risk factor for primary sjogren s syndrome
The Journal of Rheumatology, 2012Co-Authors: Johannes C Nossent, Maureen Rischmueller, Susan LesterAbstract:Objective. Immune complexes play an important role in the pathogenesis of primary Sjogren’s syndrome (pSS). Crosslinking of the neutrophil-specific Fc-γ receptor 3b (FCGR3B) facilitates immune complex clearance, and copy number variation (CNV) of the FCGR3B gene is known to reduce the uptake, and potentially clearance, of circulating immune complexes. Our objective was to determine whether FCGR3B CNV is a risk factor for pSS. Methods. This was a cross-sectional study of patients with established pSS (n = 174) and population-matched controls (n = 162). FCGR3B CNV was determined by a quantitative real-time polymerase chain reaction assay, using genomic DNA as template and Taqman chemistry. Reactions were performed as a duplex, with RNAse P as the reference gene. Clinical and serological data were analyzed for their association with FCGR3B copy number (CN). Results. Low FCGR3B CN (< 2 copies) was a risk factor for pSS in this cohort (p = 0.016), and combined results from this and a previous study yielded an overall OR of 2.3 (95% CI 1.3, 3.9, p = 0.003). Among patients with pSS in our cohort, low FCGR3B CN was not associated with anti-Ro ± La autoantibodies, but was associated with lower rheumatoid factor titers (p = 0.001) and serum IgG levels (p = 0.031). Conclusion. We confirmed that, similarly to other systemic autoimmune diseases, FCGR3B CN is a genetic susceptibility factor for pSS. As in rheumatoid arthritis, the mechanism does not appear to be related to seropositivity for characteristic autoantibodies.
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Low Copy Number of the Fc-γ Receptor 3B Gene FCGR3B Is a Risk Factor for Primary Sjögren’s Syndrome
The Journal of Rheumatology, 2012Co-Authors: Johannes C Nossent, Maureen Rischmueller, Susan LesterAbstract:Objective. Immune complexes play an important role in the pathogenesis of primary Sjogren’s syndrome (pSS). Crosslinking of the neutrophil-specific Fc-γ receptor 3b (FCGR3B) facilitates immune complex clearance, and copy number variation (CNV) of the FCGR3B gene is known to reduce the uptake, and potentially clearance, of circulating immune complexes. Our objective was to determine whether FCGR3B CNV is a risk factor for pSS. Methods. This was a cross-sectional study of patients with established pSS (n = 174) and population-matched controls (n = 162). FCGR3B CNV was determined by a quantitative real-time polymerase chain reaction assay, using genomic DNA as template and Taqman chemistry. Reactions were performed as a duplex, with RNAse P as the reference gene. Clinical and serological data were analyzed for their association with FCGR3B copy number (CN). Results. Low FCGR3B CN (< 2 copies) was a risk factor for pSS in this cohort (p = 0.016), and combined results from this and a previous study yielded an overall OR of 2.3 (95% CI 1.3, 3.9, p = 0.003). Among patients with pSS in our cohort, low FCGR3B CN was not associated with anti-Ro ± La autoantibodies, but was associated with lower rheumatoid factor titers (p = 0.001) and serum IgG levels (p = 0.031). Conclusion. We confirmed that, similarly to other systemic autoimmune diseases, FCGR3B CN is a genetic susceptibility factor for pSS. As in rheumatoid arthritis, the mechanism does not appear to be related to seropositivity for characteristic autoantibodies.
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Fc-Gamma Receptor 3B Copy Number Variation Is Not a Risk Factor for Behçet's Disease.
International Journal of Rheumatology, 2012Co-Authors: Rachel J. Black, Susan Lester, Catherine L Hill, E. Dunstan, Farhad Shahram, Abdolhadi Nadji, Noushin Bayat, Kayvan Saeedfar, N Ziaei, Maureen RischmuellerAbstract:Behcet’s disease (BD) is an immune-mediated systemic vasculitis associated with HLAB51. Other gene associations are likely and may provide further insight into the pathogenesis of this disease. Fc-gamma receptors play an important role in regulating immune function. Copy number variation (CNV) of the Fc-gamma receptor 3B (FCGR3B) gene is associated with other inflammatory conditions and may also play a role in BD. The aim of this study was to determine whether CNV of the FCGR3B gene is associated with BD or its clinical features. FCGR3B copy number was determined for 187 Iranian patients and 178 ethnicity-matched controls using quantitative real-time PCR. The genotype frequencies were comparable in both BD patients and controls. The odds ratio for low copy number ( 2CN) was 0.75 (
Neusa Pereira Da Silva - One of the best experts on this subject based on the ideXlab platform.
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fc gamma receptor iiib polymorphism and systemic lupus erythematosus association with disease susceptibility and identification of a novel FCGR3B 01 variant
Lupus, 2016Co-Authors: Viviane Cardoso Dos Santos, Marcelle Grecco, Kaline Medeiros Costa Pereira, Claudia Naufel Terzian, Luis Eduardo Coelho Andrade, Neusa Pereira Da SilvaAbstract:ObjectiveThe objective of this study was to evaluate the association between Fc gamma receptor IIIb polymorphism and susceptibility to systemic lupus erythematosus and clinical traits of the disease.MethodsGenomic DNA was obtained from 303 consecutive systemic lupus erythematosus patients and 300 healthy blood donors from the southeastern region of Brazil. The polymorphic region of the FCGR3B gene was sequenced and the alleles FCGR3B*01, FCGR3B*02 and FCGR3B*03 were analyzed.ResultsThe FCGR3B*01 allele was more frequent in systemic lupus erythematosus patients (43.1%) while the FCGR3B*02 allele prevailed among controls (63.7%) (P = 0.001). The FCGR3B*03 allele was found equally in both groups. The FCGR3B*01/*01 (20.7%) and FCGR3B*01/*02 (41.1%) genotypes were more frequent among systemic lupus erythematosus patients (P = 0.028 and P = 0.012, respectively) while the FCGR3B*02/*02 genotype was more frequent in controls (45.5%) (P < 0.001). One variant of the FCGR3B*01 allele previously described in Germany ...
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Fc gamma receptor IIIb polymorphism and systemic lupus erythematosus: association with disease susceptibility and identification of a novel FCGR3B*01 variant:
Lupus, 2016Co-Authors: Viviane Cardoso Dos Santos, Claudia Naufel Terzian, Marcelle Grecco, Kaline Medeiros Costa Pereira, Luis Eduardo Coelho Andrade, Neusa Pereira Da SilvaAbstract:ObjectiveThe objective of this study was to evaluate the association between Fc gamma receptor IIIb polymorphism and susceptibility to systemic lupus erythematosus and clinical traits of the disease.MethodsGenomic DNA was obtained from 303 consecutive systemic lupus erythematosus patients and 300 healthy blood donors from the southeastern region of Brazil. The polymorphic region of the FCGR3B gene was sequenced and the alleles FCGR3B*01, FCGR3B*02 and FCGR3B*03 were analyzed.ResultsThe FCGR3B*01 allele was more frequent in systemic lupus erythematosus patients (43.1%) while the FCGR3B*02 allele prevailed among controls (63.7%) (P = 0.001). The FCGR3B*03 allele was found equally in both groups. The FCGR3B*01/*01 (20.7%) and FCGR3B*01/*02 (41.1%) genotypes were more frequent among systemic lupus erythematosus patients (P = 0.028 and P = 0.012, respectively) while the FCGR3B*02/*02 genotype was more frequent in controls (45.5%) (P
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FCGR3B gene variants in brazilians new alleles should be considered
Blood, 2013Co-Authors: Viviane Cardoso Dos Santos, Neusa Pereira Da Silva, Claudia Naufel Terzian, Luiz Eduardo Coelho Andrade, Akemi Kuroda Chiba, Jose Orlando BordinAbstract:Background FCGR3B gene encoding the receptor FcγRIIIb has three polymorphic forms ( FCGR3B*01 , FCGR3B*02 and FCGR3B*03 ) which represent the human neutrophil antigens HNA-1a, -1b and -1c, respectively. It has been postulated that variants of these alleles might represent new FCGR3B alleles, however there are few studies assessing the frequency of such variants in different populations. In this study we performed an analysis of the frequency of the FCGR3B alleles and its variant forms examining the polymorphic region of the FCGR3B gene in a large Brazilian population sample including healthy blood donors and patients with systemic lupus erythematosus (SLE). Study Design and Methods A segment containing the polymorphic nucleotide positions 141, 147, 227, 266 and 277 in exon 3 was sequenced from genomic DNA of 615 individuals including 310 blood donors and 305 patients with SLE. Additionally, nucleotide databases were screened for variant FCGR3B sequences. Results The allele frequencies for FCGR3B*01, FCGR3B*02 and FCGR3B*03 were 0.37, 0.59 and 0.04, respectively. In two patients with SLE (0.3%) there was no gene amplification characterizing the FCGR3B-null phenotype. Considering the 5 FCGR3B polymorphic sites, 4 variant forms were observed. One variant was linked to the FCGR3B*01 allele with SNPs occurring simultaneously in two positions: A227G and G277A (n=2; 0.3%). The other three variants, linked to the FCGR3B*02 allele were: A277G (n=8; 1.3%); C141G (n=3; 0.5%); and T147C (n=1; 0.2%). All mutations observed were missenses. The results are summarized in the Table. In 103/613 (16.8%) sequenced individuals we found 19 SNPs on 14 polymorphic sites distinct from those which characterize the FCGR3B alleles. Among the most frequent, T230A was observed in 36 cases (5.9%), T230G in 20 cases (3.3%), G249A in 6 cases (1%) and C337A in 6 cases (1%), all shown as heterozygous. The comparative analysis between the two groups of individuals revealed an association between the presence of the allele FCGR3B*01 and the HNA-1a/a and HNA-1a/b genotypes with increased susceptibility to SLE (p Discussion The observed frequencies of the FCGR3B*01 , FCGR3B*02 , and FCGR3B*03 alleles were similar to those reported by genotyping studies which included Europeans or North Americans individuals. The frequency of the null phenotype (0.3%) was similar to that reported by Europeans (0.2-0.8%). The variant FCGR3B*02A277G showed a frequency (1.3%) sufficiently high to be considered a new allele as proposed by the last Granulocyte Working Party/ISBT 2013. Interestingly, this variant was significantly more prevalent in patients with SLE than in blood donors (p=0.03). All the variants described in this study have been observed in different populations however we emphasize the presence of SNPs (T230A, T230G, G249A and C337A) in polymorphic sites different from those that characterize the FCGR3B gene alleles. We conclude that the FCGR3B gene is highly polymorphic and that the occurrence of new alleles must be considered, however the functional consequences of such changes has not yet been elucidated. Disclosures: No relevant conflicts of interest to declare.
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FCGR3B 03 allele inheritance pattern in brazilian families and some new variants of gene FCGR3B
Transfusion, 2012Co-Authors: Claudia Naufel Terzian, Akemi K Chiba, Viviani C Santos, Neusa Pereira Da Silva, Jose Orlando BordinAbstract:BACKGROUND: The FCGR3B gene encoding the FcyRIIIb receptor for immunoglobulin G has three polymorphic forms known as HNA-1a, HNA-1b, and HNA-1c, encoded by the alleles FCGR3B*01, FCGR3B*02, and FCGR3B*03, respectively. It is not clear whether the inheritance of the FCGR3B*03 allele, which encodes the HNA-1c, is linked or not to the other two alleles. The objective of this study was to identify the inheritance pattern of the FCGR3B*03 allele in Brazilians. STUDY DESIGN AND METHODS: Blood samples from nine families with at least one FCGR3B*03(+) member, totalizing 47 individuals, were studied. The presence of the FCGR3B*01, FCGR3B*02, and FCGR3B*03 alleles was detected by the polymerase chain reaction with sequence-specific priming method, and all DNA samples were sequenced. RESULTS: In three of the nine studied families, the FCGR3B*03 was passed down with the FCGR3B*02, while in one family the FCGR3B*03 was inherited in linkage with FCGR3B*01. The other families were not informative regarding FCGR3B*03 inheritance. Sequencing showed for the first time one single-nucleotide polymorphism at Position 264 resulting from a simple substitution CT; three other different substitutions at Position 230, TA, TG; and the presence of three nucleotides at Position 230 (T, G, and A). The previously reported variants FCGR3B*01A227G and FCGR3BG330T were also found. CONCLUSION: In this Brazilian FCGR3B*03(+) group we found that the inheritance of FCGR3B*03 took place by a linkage to FCGR3B*02 or to FCGR3B*01. Linkage of FCGR3B*03 to FCGR3B*02 was the most common. Additionally, we report SNPs that have not been described, suggesting that they might be more common than previously thought.
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FCGR3B*03 allele inheritance pattern in Brazilian families and some new variants of gene FCGR3B
Transfusion, 2011Co-Authors: Claudia Naufel Terzian, Akemi K Chiba, Viviani C Santos, Neusa Pereira Da Silva, Jose Orlando BordinAbstract:BACKGROUND: The FCGR3B gene encoding the FcyRIIIb receptor for immunoglobulin G has three polymorphic forms known as HNA-1a, HNA-1b, and HNA-1c, encoded by the alleles FCGR3B*01, FCGR3B*02, and FCGR3B*03, respectively. It is not clear whether the inheritance of the FCGR3B*03 allele, which encodes the HNA-1c, is linked or not to the other two alleles. The objective of this study was to identify the inheritance pattern of the FCGR3B*03 allele in Brazilians. STUDY DESIGN AND METHODS: Blood samples from nine families with at least one FCGR3B*03(+) member, totalizing 47 individuals, were studied. The presence of the FCGR3B*01, FCGR3B*02, and FCGR3B*03 alleles was detected by the polymerase chain reaction with sequence-specific priming method, and all DNA samples were sequenced. RESULTS: In three of the nine studied families, the FCGR3B*03 was passed down with the FCGR3B*02, while in one family the FCGR3B*03 was inherited in linkage with FCGR3B*01. The other families were not informative regarding FCGR3B*03 inheritance. Sequencing showed for the first time one single-nucleotide polymorphism at Position 264 resulting from a simple substitution CT; three other different substitutions at Position 230, TA, TG; and the presence of three nucleotides at Position 230 (T, G, and A). The previously reported variants FCGR3B*01A227G and FCGR3BG330T were also found. CONCLUSION: In this Brazilian FCGR3B*03(+) group we found that the inheritance of FCGR3B*03 took place by a linkage to FCGR3B*02 or to FCGR3B*01. Linkage of FCGR3B*03 to FCGR3B*02 was the most common. Additionally, we report SNPs that have not been described, suggesting that they might be more common than previously thought.
Susan Lester - One of the best experts on this subject based on the ideXlab platform.
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No Association between FCγR3B Copy Number Variation and Susceptibility to Biopsy-Proven Giant Cell Arteritis
Arthritis, 2013Co-Authors: E. Dunstan, Maureen Rischmueller, Susan Lester, Rachel J. Black, Helen H.l. Chan, Alex W. Hewitt, Catherine L HillAbstract:Objective. To determine the relationship between FCGR3B gene copy number variation (CNV) and biopsy proven giant cell arteritis (GCA). Methods. FCGR3B CNV was determined in 139 Australian biopsy proven GCA patients and 162 population matched controls, using a duplex qPCR assay and RNase P as the reference gene. Copy number was determined using Copy Caller software (v.1.0, Applied Biosystems, USA). CNV genotypes were classified into 3 groups (
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susceptibility for lupus nephritis by low copy number of the FCGR3B gene is linked to increased levels of pathogenic autoantibodies
Autoimmune Diseases, 2013Co-Authors: Johannes C Nossent, Andrea Beckermerok, Maureen Rischmueller, Susan LesterAbstract:Low copy number (CN) of the FCGR3B gene reduces FCGR3B membrane expression on neutrophils and results in clearance of a smaller amount of immune complex. We investigated FCGR3B CN in relation to the clinical phenotype in a Caucasian SLE cohort (n = 107). FCGR3B CN was determined by three different qPCR parameter estimations (Ct−, Cy0, and cpD1) and confirmed by the FCGR2C/FCGR2A paralog ratio test. Clinical and serological data were then analyzed for their association with FCGR3B CN. Low FCGR3B CN ( 2). In multivariate analyses, LN was independently associated with anti-C1q-Ab levels (P = 0.03) and low FCGR3B CN (P = 0.09). We conclude that the susceptibility for LN in patients with low FCGR3B CN is linked to increased levels of pathogenic autoantibodies.
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low copy number of the fc γ receptor 3b gene FCGR3B is a risk factor for primary sjogren s syndrome
The Journal of Rheumatology, 2012Co-Authors: Johannes C Nossent, Maureen Rischmueller, Susan LesterAbstract:Objective. Immune complexes play an important role in the pathogenesis of primary Sjogren’s syndrome (pSS). Crosslinking of the neutrophil-specific Fc-γ receptor 3b (FCGR3B) facilitates immune complex clearance, and copy number variation (CNV) of the FCGR3B gene is known to reduce the uptake, and potentially clearance, of circulating immune complexes. Our objective was to determine whether FCGR3B CNV is a risk factor for pSS. Methods. This was a cross-sectional study of patients with established pSS (n = 174) and population-matched controls (n = 162). FCGR3B CNV was determined by a quantitative real-time polymerase chain reaction assay, using genomic DNA as template and Taqman chemistry. Reactions were performed as a duplex, with RNAse P as the reference gene. Clinical and serological data were analyzed for their association with FCGR3B copy number (CN). Results. Low FCGR3B CN (< 2 copies) was a risk factor for pSS in this cohort (p = 0.016), and combined results from this and a previous study yielded an overall OR of 2.3 (95% CI 1.3, 3.9, p = 0.003). Among patients with pSS in our cohort, low FCGR3B CN was not associated with anti-Ro ± La autoantibodies, but was associated with lower rheumatoid factor titers (p = 0.001) and serum IgG levels (p = 0.031). Conclusion. We confirmed that, similarly to other systemic autoimmune diseases, FCGR3B CN is a genetic susceptibility factor for pSS. As in rheumatoid arthritis, the mechanism does not appear to be related to seropositivity for characteristic autoantibodies.
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Low Copy Number of the Fc-γ Receptor 3B Gene FCGR3B Is a Risk Factor for Primary Sjögren’s Syndrome
The Journal of Rheumatology, 2012Co-Authors: Johannes C Nossent, Maureen Rischmueller, Susan LesterAbstract:Objective. Immune complexes play an important role in the pathogenesis of primary Sjogren’s syndrome (pSS). Crosslinking of the neutrophil-specific Fc-γ receptor 3b (FCGR3B) facilitates immune complex clearance, and copy number variation (CNV) of the FCGR3B gene is known to reduce the uptake, and potentially clearance, of circulating immune complexes. Our objective was to determine whether FCGR3B CNV is a risk factor for pSS. Methods. This was a cross-sectional study of patients with established pSS (n = 174) and population-matched controls (n = 162). FCGR3B CNV was determined by a quantitative real-time polymerase chain reaction assay, using genomic DNA as template and Taqman chemistry. Reactions were performed as a duplex, with RNAse P as the reference gene. Clinical and serological data were analyzed for their association with FCGR3B copy number (CN). Results. Low FCGR3B CN (< 2 copies) was a risk factor for pSS in this cohort (p = 0.016), and combined results from this and a previous study yielded an overall OR of 2.3 (95% CI 1.3, 3.9, p = 0.003). Among patients with pSS in our cohort, low FCGR3B CN was not associated with anti-Ro ± La autoantibodies, but was associated with lower rheumatoid factor titers (p = 0.001) and serum IgG levels (p = 0.031). Conclusion. We confirmed that, similarly to other systemic autoimmune diseases, FCGR3B CN is a genetic susceptibility factor for pSS. As in rheumatoid arthritis, the mechanism does not appear to be related to seropositivity for characteristic autoantibodies.
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Fc-Gamma Receptor 3B Copy Number Variation Is Not a Risk Factor for Behçet's Disease.
International Journal of Rheumatology, 2012Co-Authors: Rachel J. Black, Susan Lester, Catherine L Hill, E. Dunstan, Farhad Shahram, Abdolhadi Nadji, Noushin Bayat, Kayvan Saeedfar, N Ziaei, Maureen RischmuellerAbstract:Behcet’s disease (BD) is an immune-mediated systemic vasculitis associated with HLAB51. Other gene associations are likely and may provide further insight into the pathogenesis of this disease. Fc-gamma receptors play an important role in regulating immune function. Copy number variation (CNV) of the Fc-gamma receptor 3B (FCGR3B) gene is associated with other inflammatory conditions and may also play a role in BD. The aim of this study was to determine whether CNV of the FCGR3B gene is associated with BD or its clinical features. FCGR3B copy number was determined for 187 Iranian patients and 178 ethnicity-matched controls using quantitative real-time PCR. The genotype frequencies were comparable in both BD patients and controls. The odds ratio for low copy number ( 2CN) was 0.75 (
Hong Zhang - One of the best experts on this subject based on the ideXlab platform.
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copy number variation of fcgr3a rather than FCGR3B and fcgr2b is associated with susceptibility to anti gbm disease
International Immunology, 2010Co-Authors: Xujie Zhou, Jicheng Lv, Dingfang Bu, Lei Yu, Yanrong Yang, Juan Zhao, Rui Yang, Minghui Zhao, Hong ZhangAbstract:Anti-glomerular basement membrane antibody disease (anti-GBM disease) is a rare disorder characteristic of universally poor outcome. Fcg receptors (FcgRs) play important roles in anti-GBM disease based on evidence from animal models. Copy number variation (CNV) influences disease susceptibility. The FcgRs genes show CNV, and CNV of the FCGR3B gene is associated with glomerulonephritis in systemic lupus erythematosus and anti-neutrophil cytoplasmic antibodyassociated small vasculitis. Here, we investigated CNV of three FCGR genes, including two (FCGR3A and FCGR3B) for activating FcgRs and one (FCGR2B) for inhibitory FcgR by duplex quantitative realtime PCR. Copy numbers were analyzed by Applied Biosystems CopyCaller Software v1.0. We first demonstrated the distribution of CNV of FCGR3A, FCGR3B and no CNV of FCGR2B in Chinese population (including 47 anti-GBM patients and 146 healthy controls). The frequency of CNV of FCGR3A was observed to be significantly higher than matched healthy controls (27.7 versus 12.3%, P 5 0.013, odds ratio 1.21‐6.10). Considering previous report about gene knock-out animal models and CNV effect of FCGR3A, we thus propose that CNV in members of FCGR family should have different roles in the pathogenesis of human anti-GBM disease.
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fcgr2b gene polymorphism rather than fcgr2a fcgr3a and FCGR3B is associated with anti gbm disease in chinese
Nephrology Dialysis Transplantation, 2010Co-Authors: Xujie Zhou, Lei Yu, Juan Zhao, Rui Yang, Minghui Zhao, L V Jicheng, Hong ZhangAbstract:Background. The Fcγ receptors play important roles in anti-glomerular basement membrane antibody disease (anti-GBM disease) in animal models, and FCGR gene polymorphisms have been reported to be associated with numerous human autoimmune diseases. We aimed to clarify the genetic association of FCGR gene polymorphisms with anti-GBM disease in Chinese patients. Methods. A total of 48 patients with anti-GBM disease and 225 geographically and ethnically matched healthy controls were involved. Genotyping of the previously identified polymorphisms FCGR2A131H/R (rs1801274), FCGR2B 232I/T (rs1050501) and FCGR3A176F/V (rs396991) were detected by the TaqMan genotyping assay and FCGR3B NA1/2 by the PCR-sequence specific primer (SSP). Allele type, genotype and haplotype of identified polymorphisms were analysed between patients and controls. Results. Our results revealed that FCGR2A131H/R, FCGR3A176F/V and FCGR3B NA1/2 were not associated with anti-GBM disease. The frequency of the FCGR2B 232T allele (30.2% versus 15.6%, corrected P = 0.00028, 95% CI: 1.42–3.89) and genotypes of I232T (60.4% versus 31.1%, corrected P = 0.0004, 95% CI: 1.78–6.43) was significantly increased in patients compared with controls. Conclusion. The present study demonstrates the genetic association of polymorphism ofFCGR2B (I232T) with susceptibility to anti-GBM disease in Chinese.
