{{Rsnum
|rsid=396991
|Gene=FCGR3A
|Chromosome=1
|position=161544752
|Orientation=minus
|ReferenceAllele=T
|MissenseAllele=G
|GMAF=0.2447
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(G;G)
|geno2=(G;T)
|geno3=(T;T)
|Gene_s=FCGR3A
}}{{ population diversity
| geno1=(G;G)
| geno2=(G;T)
| geno3=(T;T)
| CEU | 0.0 | 0.0 | 0.0
| HCB | 70.5 | 29.5 | 0.0
| JPT | 59.1 | 38.6 | 2.3
| YRI | 0.0 | 0.0 | 0.0
| ASW | 0.0 | 0.0 | 0.0
| CHB | 70.5 | 29.5 | 0.0
| CHD | 0.0 | 0.0 | 0.0
| GIH | 0.0 | 0.0 | 0.0
| LWK | 0.0 | 0.0 | 0.0
| MEX | 0.0 | 0.0 | 0.0
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 0.0 | 0.0
| HapMapRevision=28
}}[[rs396991]] is a SNP in the Fc fragment of IgG, low affinity IIIa, receptor (CD16a) [[FCGR3A]] gene. [[rs396991]](T) encodes the phenylalanine (F) allele, with the (G) allele encoding the variant valine (V). The (V) isoform is considered high-binding to IgG1 and IgG3, while the (F) isoform is considered low-binding. This SNP is known in the literature by many names, including A559C, T559G, 158F/V, and 176F/V.{{PMID|9276722|OA=1
}}

What's the importance of this? FcgRIIIa stimulatory receptors are expressed by most cells in the immune system, including monocytes, dendritic cells, macrophages, natural killer cells, platelets and endothelial cells, as well as a subpopulation of T-cells. FcgR isoforms have been linked to the pathogenic consequences triggered by autoantibodies or immune complexes in autoimmune diseases such as [[rheumatoid arthritis]] (RA) and [[systemic lupus erythematosus]] (SLE), as well as to the efficacy of some immunotherapeutic treatments such as [[rituximab]].

Many studies have been published about this FCGR3A SNP, roughly divided by either disorder or treatment as follows:

* HIV to AIDs, including susceptibility and progression:
** In a study of 2 cohorts of men infected with [[HIV]], the [[rs396991]](T;T) (ie F/F) genotype was underrepresented in patients with Kaposi's sarcoma, whereas the heterozygous genotype was associated with it's development. A similar association was observed between [[rs396991]] genotypes and human herpesvirus-8 (HHV-8) seropositivity.{{PMID|10733511}}

* Crohn's disease
** A study of 300+ patients with [[Crohn's disease]] determined that the [[rs396991]](T) allele had an odds ratio of 1.58 (CI: 1.06-2.35) and the (G;T) genotype an odds ratio of 1.64 (CI: 1.08-2.5) for the disease.{{PMID|17600378}}

* Rheumatoid arthritis
** Meta-analysis of 10 different studies concluded that amongst European subjects (and not Asians), the VV ([[rs396991]](G;G)) genotype was associated with increased risk for [[rheumatoid arthritis]], with an odds ratio of 1.374 (CI: 1.101-1.714, p = 0.005) as compared to the FF genotype.{{PMID|18843786}}
** Although [[rs396991]] is unlikely to play a major role by itself in susceptibility to [[rheumatoid arthritis]], the presence of the [[rs396991]](G) high-binding allele may predispose shared epitope positive individuals to the disease.{{PMID|12734884}}

Classifying the reports by immunotherapeutic treatment studied yields the following:

* Studies involving [[rituximab]]:
** In a study of ~200 Korean patients, the FCGR3A valine (V) allele was significantly correlated with a higher complete response rate to rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy compared with the phenylalanine (F) allele (88% in V/V vs 79% in V/F vs 50% in F/F; p = .002), although it did not correlate with survival in patients with [[diffuse large B-cell lymphoma]] (DLBCL).{{PMID|16609067}}
** In a study of 58 Croatian patients with diffuse large B-cell lymphoma, [[rs396991]] did not influence response, event-free or overall survival.{{PMID|17606457}}
** A study of 49 patients receiving [[rituximab]] for previously untreated follicular [[non-Hodgkin's lymphoma]] concluded that [[rs396991]](G;G) patients have a 75% to 90% chance of experiencing a clinical response to rituximab monotherapy, whereas patients with at least one [[rs396991]](T) allele have a 25% to 51% chance of responding.{{PMID|11806974}}
** Another study of 89 patients with follicular lymphoma found that [[rs396991]] genotype was associated with the response rate and freedom from progression after treatment with [[rituximab]]. {{PMID|12975461}}

* Studies involving [[cetuximab]]:
** In a study of 39 patients with metastatic [[colorectal cancer]] treated with [[cetuximab]], the [[rs396991]](G) (ie F) allele was associated with longer progression-free survival (PFS; p = 0.055), by perhaps 1-2 months.{{PMID|17704420}}

{{PMID Auto
|PMID=19140833
|Title=Linkage and association study of FcgammaR polymorphisms in celiac disease
}}
{{PMID Auto
|PMID=19640933
|Title=FCGR2B gene polymorphism rather than FCGR2A, FCGR3A and FCGR3B is associated with anti-GBM disease in Chinese
}}

{{PharmGKB
|RSID=rs396991
|Name_s=FCGR3A: V158F; 158F/V; 158V/F
|Gene_s=FCGR3A
|Feature=
|Evidence=PubMed ID:19019892
|Annotation=This variant was associated with risk to anti-citrullinated peptide antibodies (ACPA)-positive rheumatoid arthritis, and the association increased slightly after correction for CNV of the FcgammaRIIIA-gene. The W genotype was more prevalent in cases than controls.
|Drugs=
|Drug Classes=
|Diseases=Arthritis, Rheumatoid
|Curation Level=Curated
|PharmGKB Accession ID=PA164934773
}}
{{PMID Auto
|PMID=20149216
|Title=Fcgamma receptor polymorphisms and their association with periodontal disease: a meta-analysis
}}
{{PMID Auto
|PMID=20439102
|Title=Analysis of MIF, FCGR2A and FCGR3A gene polymorphisms with susceptibility to pulmonary tuberculosis in Moroccan population
}}

{{PharmGKB
|RSID=rs396991
|Name_s=FCGR3A: V158F; 158F/V; 158V/F; 176F/V; A559C; T559G
|Gene_s=FCGR3A
|Feature=
|Evidence=PubMed ID:12975461; PubMed ID:16609067; PubMed ID:19018870
|Annotation=The FCGR3A valine (V) allele was significantly correlated with a higher complete response rate to R-CHOP (rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone) compared with the phenylalanine (F) allele in a study of ~200 Korean patients with diffuse large B-cell lymphoma. In a study of Japanese patients with non-hodgekin's lymphoma, the F/F homozygotes had significantly reduced levels of IgG compared to the patients with F/V or V/V alleles after APBSCT and adjuvant rituximab therapy. This variant was also associated with the response rate to rituximab and freedom from progression in patients with follicular lymphoma.
|Drugs=rituximab
|Drug Classes=
|Diseases=Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, Large-Cell, Diffuse; Lymphoma, Non-Hodgkin
|Curation Level=Curated
|PharmGKB Accession ID=PA162363687
}}

{{PharmGKB
|RSID=rs396991
|Name_s=FCGR3A: V158F; 158F/V; 158V/F; 176F/V; A559C; T559G
|Gene_s=FCGR3A
|Feature=
|Evidence=PubMed ID:19005160
|Annotation=This variant may be a useful marker to predict response to infliximab in Japanese patients with rheumatoid arthritis.
|Drugs=infliximab
|Drug Classes=
|Diseases=Arthritis, Rheumatoid
|Curation Level=Curated
|PharmGKB Accession ID=PA162363688
}}

{{PharmGKB
|RSID=rs396991
|Name_s=FCGR3A: V158F; 158F/V; 158V/F; 176F/V; A559C; T559G
|Gene_s=FCGR3A
|Feature=
|Evidence=PubMed ID:18843786
|Annotation=This variant is associated with susceptibility to rheumatoid arthritis in meta analysis of 10 studies. In subjects of European descent, the V/V (G/G) genotype carriers was associated with increased risk for rheumatoid arthritis as compared to the F/F genotype carriers. This association was not found in Asians.
|Drugs=
|Drug Classes=
|Diseases=Arthritis, Rheumatoid
|Curation Level=Curated
|PharmGKB Accession ID=PA162363685
}}

{{PharmGKB
|RSID=rs396991
|Name_s=FCGR3A: V158F; 158F/V; 158V/F; 176F/V; A559C; T559G
|Gene_s=FCGR3A
|Feature=
|Evidence=PubMed ID:9276722
|Annotation=This variant alters ligand binding ability of the receptor (FCGR3A/CD16) and may predispose individuals carrying the variant to autoimmune diseases. The V/V homozygotes (high-binding) bound more IgG1 and IgG3 than F/F homozygotes.
|Drugs=
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA162363686
}}

{{PharmGKB
|RSID=rs396991
|Name_s=FCGR3A: V158F; 158F/V; 158V/F; 176F/V; A559C; T559G
|Gene_s=FCGR3A
|Feature=
|Evidence=PubMed ID:17704420
|Annotation=This variant was associated with response to cetuximab in colorectal cancer patients. The F allele carriers was associated with longer progression-free survival.
|Drugs=cetuximab
|Drug Classes=
|Diseases=Colorectal Neoplasms
|Curation Level=Curated
|PharmGKB Accession ID=PA162363689
}}
{{PMID Auto
|PMID=21208440
|Title=Polymorphisms of CD16A and CD32 Fcgamma Receptors and Circulating Immunocomplexes in Meniere Disease: a case-control study
|OA=1
}}
{{PMID Auto
|PMID=21723269
|Title=Genetic profiling of GSTP1, DPYD, FCGR2A, FCGR3A and CCND1 genes in an Argentinian population
}}{{PMID Auto
|PMID=18759263
|Title=Features associated with, and the impact of, hemolytic anemia in patients with systemic lupus erythematosus: LX, results from a multiethnic cohort.
|OA=1
}}

{{PMID Auto
|PMID=19421223
|Title=Fcgamma receptors: structure, function and role as genetic risk factors in SLE.
|OA=1
}}

{{PMID Auto
|PMID=20018222
|Title=Association of polymorphism in FcGR3A gene and progression of low-grade precursor lesions of cervical carcinoma.
}}

{{PMID Auto
|PMID=20400988
|Title=A single-nucleotide polymorphism of the Fcgamma receptor type IIIA gene in the recipient predicts transplant outcomes after HLA fully matched unrelated BMT for myeloid malignancies.
}}

{{PMID Auto
|PMID=20508037
|Title=Copy number, linkage disequilibrium and disease association in the FCGR locus.
|OA=1
}}

{{PMID Auto
|PMID=22417159
|Title=DNA sequence variation and regulation of genes involved in pathogenesis of pulmonary tuberculosis.
}}
{{PMID Auto
|PMID=23075294
|Title=Association of the FCGR3A-158F/V Gene Polymorphism with the Response to Rituximab Treatment in Spanish Systemic Autoimmune Disease Patients
}}{{GET Evidence
|gene=FCGR3A
|aa_change=Phe212Val
|aa_change_short=F212V
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs396991
|overall_frequency_n=3065
|overall_frequency_d=10758
|overall_frequency=0.284904
|n_genomes=26
|n_genomes_annotated=0
|n_haplomes=31
|n_articles=5
|n_articles_annotated=4
|in_pharmgkb=Y
|nblosum100=3
|autoscore=1
|webscore=N
}}
{{PMID Auto
|PMID=23680410
|Title=Detection of the FCGR3a polymorphism using a real-time polymerase chain reaction assay
}}
{{PMID Auto
|PMID=24375423
|Title=FcγRIIIa SNPs and haplotypes affect human IgG binding and association with lupus nephritis in African Americans
}}
{{PMID Auto
|PMID=24586589
|Title=Functional fcgamma receptor polymorphisms are associated with human allergy
|OA=1
}}{{PMID Auto
|PMID=22922574
|Title=Fcgamma receptor polymorphisms do not predict response to intravenous immunoglobulin in myasthenia gravis.
}}

{{PMID Auto
|PMID=23649770
|Title=Associations between FCGR2A rs1801274, FCGR3A rs396991, FCGR3B NA1/NA2 polymorphisms and periodontitis: a meta-analysis.
}}
{{PMID Auto
|PMID=24782186
|Title=Fcγ Receptor IIIa Single-Nucleotide Polymorphisms and Haplotypes Affect Human IgG Binding and Are Associated With Lupus Nephritis in African Americans
}}