FcγRIIB, the only inhibitory IgG Fc receptor, functions to suppress the hyper-activation of immune cells. Numerous studies have illustrated its inhibitory function through the ITIM motif in the cytoplasmic tail of FcγRIIB. However, later studies revealed that in addition to the ITIM, the transmembrane (TM) domain of FcγRIIB is also indispensable for its inhibitory function. Indeed, recent epidemiological studies revealed that a non-synonymous single nucleotide polymorphism (rs1050501) within the TM domain of FcγRIIB, responsible for the I232T substitution, is associated with the susceptibility to systemic lupus erythematosus (SLE). In this review, we will summarize these epidemiological and functional studies of FcγRIIB-I232T in the past few years, and will further discuss the mechanisms accounting for the functional loss of FcγRIIB-I232T. Our review will help the reader gain a deeper understanding of the importance of the TM domain in mediating the inhibitory function of FcγRIIB and may provide insights to a new therapeutic target for the associated diseases.
Autoimmune Diseases ; drug therapy ; genetics ; immunology ; Humans ; Protein Domains ; Receptors, IgG ; chemistry ; immunology

High-dose intravenous immunoglobulins alter the disease activity of adult-onset Still's disease (AOSD). Because activation status of FcgammaR is possibly dependent on their genetic polymorphisms, we investigated whether the polymorphisms of FcgammaR IIa and IIIa are risk factors, and affect the clinical features of AOSD. Genomic DNA was extracted from 36 patients and from 197 healthy controls. Polymerase chain reaction for FcgammaR IIa and IIIa using the allele-specific primers and direct sequencing of FcgammaR IIIa polymorphic site were performed. The frequencies of FcgammaR IIa/IIIa genotype between patients with AOSD and controls were not different. The allelic frequencies of FcgammaR IIa/IIIa between patients with AOSD and controls were not different, either. However, the FcgammaR IIa-R/R131 genotype was associated with a higher concentration of hemoglobin (p=0.04) and stable liver function (p=0.009) than the other genotypes. The FcgammaR IIIa-F/F176 genotype was associated with significantly lower titers of serum ferritin (p=0.025), and higher serum albumin (p=0.037) and cholesterol (p=0.014) concentrations than the other genotypes. This study suggest that the FcgammaR IIa and IIIa polymorphisms might not be genetic risk factors for AOSD in Korean, but contribute to the activity of disease. FcgammaR IIa-R/R131 and IIIa-F/F176 genotypes, low-binding genotypes for IgG2a and G1, may have more protective effects in acute stage of the disease than the other genotypes.
Adult ; Antigens, CD/*genetics ; Female ; Genotype ; Humans ; Korea ; Male ; *Polymorphism, Genetic ; Receptors, IgG/*genetics ; Still's Disease, Adult-Onset/*genetics/physiopathology

ATP-Binding Cassette Transporters ; genetics ; DNA Copy Number Variations ; genetics ; Genetic Predisposition to Disease ; Gout ; genetics ; Humans ; Receptors, IgG ; genetics ; Receptors, Interleukin-17 ; genetics

Fcγ receptorIIIa (FcγRIIIa) polymorphism was considered to influence clinical response to therapeutic monoclonal antibody (MAb) against cancer, which is suggested to affect MAb binding and MAb-dependent NK cell-mediated cytotoxicity. The purpose of this study was to examine the FcγRIIIa gene polymorphisms in healthy children and in children with hematological malignancy, and to explore its possible effect on MAb in children with hematological malignancies. 43 healthy children (H) and 20 pediatric patients with hematological malignancies (HM) were enrolled in this study. DNA was isolated from peripheral blood, and then nest-polymerase chain reaction-restriction fragment length polymorphism (nest-PCR and PCR-RFLP) was used to determine the FcγRIIIa-158 genotypes in each groups of subject, digested fragments were subjected to electrophoresis on 15% PAGE. The results showed that there were a higher frequencies of FcγRIIIa-158V/F in H and HM group (72.1% and 75.0% respectively), the frequencies of FcγRIIIa-158V/V were 27.9% and 25.0% in H and HM group respectively, but there was no FcγRIIIa-158F/F in the two groups. No significant difference in distribution of the FcγRIIIa-158 genotype was found between HM and H groups (p > 0.05). It is concluded that FcγRIIIa-158V/F is more frequent, while FcγRIIIa-158V/V is less, but FcγRIIIa-158F/F is very rare in both groups. No significant difference of FcγRIIIa polymorphism distribution is found between healthy and hematological malignancy groups.
Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Genotype ; Hematologic Neoplasms ; genetics ; Humans ; Male ; Polymorphism, Genetic ; Receptors, IgG ; genetics

To investigate the distribution of variant genotypes of Fc gamma receptor IIIa (Fc gamma R IIIa) in healthy Chinese population of Zhengzhou city, genomic DNA was extracted from peripheral blood of healthy donators. The genotypes of Fc gamma R IIIa-158 were determined by nested polymerase chain reaction (PCR) in 137 healthy people in Zhengzhou city. The results showed that frequencies of variant genotypes FF, VV and VF were 42.3%, 48.9% and 8.8% respectively. The distribution of Fc gamma R IIIa-158 in healthy Chinese population of Zhengzhou city was polymorphic and different from that of African Americans (AA) and Caucasian Americans (CA).
Asian Continental Ancestry Group ; European Continental Ancestry Group ; Genotype ; Polymerase Chain Reaction ; *Polymorphism, Genetic ; Receptors, IgG/*genetics ; Variation (Genetics)

OBJECTIVETo assess the association of several single nucleotide polymorphisms and haplotypes of the FCGR2A gene with ulcerative colitis (UC) among Chinese patients.

METHODSFor 198 UC patients and 356 healthy controls, the alleles and genotypes of the FCGR2A gene (rs1801274, rs10800309 and rs6696854) were detected with a multiplex SNaPshot technique. All subjects were also subjected to linkage disequilibrium and haplotype analyses.

RESULTSThe mutant homozygote (CC) of the FCGR2A gene rs1801274 polymorphism was less frequent among UC patients compared with the controls (5.56% vs. 11.80%, P=0.017, OR=0.440, 95%CI: 0.221-0.875). However, the allelic and genotypic distributions of other two SNPs did not differ significantly between the two groups (all P>0.05). Furthermore, no association of the three SNPs (rs1801274, rs10800309 and rs6696854) of the FCGR2A gene with the severity and location of the UC was found (all P>0.05). The three SNPs were shown to be in a strong linkage [rs1801274-rs10800309 (D'=0.863, r=0.634); rs1801274-rs6696854 (D'=0.753, r=0.546); rs10800309-rs6696854(D'=0.990, r=0.802)]. Moreover, the frequency of T-A-T haplotype was higher among the UC patients compared with the controls (67.40% vs. 60.93%, P=0.032, OR=1.326, 95%CI: 1.024-1.717).

CONCLUSIONOur findings suggested that the mutant homozygote (CC) of the FCGR2A gene (rs1801274) may have a protective role among Chinese patients with UC. Moreover, the T-A-T haplotype formed by rs1801274, rs10800309 and rs6696854 may confer a higher risk for UC.

Adult ; Asian Continental Ancestry Group ; genetics ; Colitis, Ulcerative ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Haplotypes ; genetics ; Humans ; Polymorphism, Single Nucleotide ; genetics ; Receptors, IgG ; genetics

To investigate the distribution of variant genotypes of Fc gamma receptor IIIa (Fc gamma R IIIa) in healthy Chinese population of Zhengzhou city, genomic DNA was extracted from peripheral blood of healthy donators. The genotypes of Fc gamma R IIIa-158 were determined by nested polymerase chain reaction (PCR) in 137 healthy people in Zhengzhou city. The results showed that frequencies of variant genotypes FF, VV and VF were 42.3%, 48.9% and 8.8% respectively. The distribution of Fc gamma R IIIa-158 in healthy Chinese population of Zhengzhou city was polymorphic and different from that of African Americans (AA) and Caucasian Americans (CA).
Asian Continental Ancestry Group ; European Continental Ancestry Group ; Genetic Variation ; Genotype ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Receptors, IgG ; genetics

OBJECTIVETo investigate the polymorphism of FcgammaRIIIb genotype, IgG G2m(23) factor and their associations with the susceptibility to aggressive periodontitis.

METHODSDNA of white blood cells and serum from 21 aggressive periodontitis patients and 26 healthy controls was extracted. Genotype of FcgammaRIIIb and phenotype of G2m(23) factor was determined by allele-specific PCR and dot immunobinding assay respectively.

RESULTSThe frequency of FcgammaRIIIb-NA1/NA1 genotype in aggressive periodontitis patients was significantly higher than in healthy controls (P < 0.05). The ratio of subjects with FcgammaRIIIb-NA1/NA1 genotype and positive G2m(23) factor was higher in aggressive periodontitis patients (11/21) than in health controls (5/26) (P < 0.05). However, no statistical difference in distribution of G2m(23) factor alone was observed between patients and controls.

CONCLUSIONSThis study indicates that FcgammaRIIIb-NA1/NA1 genotype may be a susceptible genotype to aggressive periodontitis in Chinese population. Subjects with FcgammaRIIIb NA1/NA1 genotype and positive G2m(23) factor may be more susceptible to aggressive periodontitis.

Adult ; Antigens, CD ; genetics ; Asian Continental Ancestry Group ; genetics ; Female ; GPI-Linked Proteins ; Genetic Predisposition to Disease ; Genotype ; Humans ; Immunoglobulin Gm Allotypes ; genetics ; Male ; Periodontitis ; genetics ; Receptors, IgG ; genetics

Behcet's disease (BD) is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent uveitis, oral and genital ulcers and skin lesions. To identify some pathogenic variants associated with severe Behcet's uveitis, we used targeted and massively parallel sequencing methods to explore the genetic diversity of target regions. A solution-based target enrichment kit was designed to capture whole-exonic regions of 132 candidate genes. Using a multiplexing strategy, 32 samples from patients with a severe type of Behcet's uveitis were sequenced with a Genome Analyzer IIx. We compared the frequency of each variant with that of 59 normal Korean controls, and selected five rare and eight common single-nucleotide variants as the candidates for a replication study. The selected variants were genotyped in 61 cases and 320 controls and, as a result, two rare and seven common variants showed significant associations with severe Behcet's uveitis (P<0.05). Some of these, including rs199955684 in KIR3DL3, rs1801133 in MTHFR, rs1051790 in MICA and rs1051456 in KIR2DL4, were predicted to be damaging by either the PolyPhen-2 or SIFT prediction program. Variants on FCGR3A (rs396991) and ICAM1 (rs5498) have been previously reported as susceptibility loci of this disease, and those on IFNAR1, MTFHR and MICA also replicated the previous reports at the gene level. The KIR3DL3 and KIR2DL4 genes are novel susceptibility genes that have not been reported in association with BD. In conclusion, this study showed that target enrichment and next-generation sequencing technologies can provide valuable information on the genetic predisposition for Behcet's uveitis.
Adult ; Aged ; Behcet Syndrome/*genetics ; Case-Control Studies ; Female ; Histocompatibility Antigens Class I/genetics ; Humans ; Intercellular Adhesion Molecule-1/genetics ; Interferon-alpha/genetics ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Receptors, IgG/genetics ; Receptors, KIR/genetics ; Receptors, KIR2DL4/genetics

BACKGROUND: Human neutrophil antigens (HNAs) are involved in autoimmune and alloimmune neutropenia and transfusion-related acute lung injury. The HNA-1 system is important in immunogenetics, and allele frequencies have been described in different populations. This study investigated the frequency of FCGR3B alleles encoding HNA-1a, HNA-1b, and HNA-1c among Thai blood donors and compared these frequencies with those previously reported for other populations. METHODS: Eight hundred DNA samples obtained from unrelated healthy blood donors at the National Blood Centre, Thai Red Cross Society, Bangkok, and the Blood Bank, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, were included. Samples were simultaneously typed for each FCGR3B allele using an in-house polymerase chain reaction with sequence-specific primer (PCR-SSP) technique. RESULTS: The frequencies of FCGR3B*1, FCGR3B*2, and FCGR3B*3 alleles in central Thai blood donors were 0.548, 0.452, and 0.004, respectively; only FCGR3B*1 and FCGR3B*2 alleles were found in northern Thai blood donors (0.68 and 0.32, respectively). Compared with other Asian populations, central Thais had higher frequencies of the FCGR3B*2 allele (P<0.001), while the frequencies of the FCGR3B*1 and FCGR3B*2 alleles in northern Thais were similar to those previously reported in Taiwanese and Japanese populations. In contrast, the frequencies of the FCGR3B*1 and FCGR3B*2 alleles in the northern Thai population were statistically different from those observed in central Thai, Korean, German, and Turkish populations. CONCLUSIONS: FCGR3B allele frequencies were significantly different between central and northern Thai blood donors. Our in-house PCR-SSP method is a simple, cost-effective, and convenient method for FCGR3B allele detection.
Asian Continental Ancestry Group/*genetics ; *Blood Donors ; DNA/analysis ; DNA Primers/chemistry/metabolism ; GPI-Linked Proteins/genetics ; Gene Frequency ; Genotype ; Humans ; Polymerase Chain Reaction ; Receptors, IgG/*genetics ; Thailand