{{Rsnum
|rsid=1801274
|Gene=FCGR2A
|Chromosome=1
|position=161509955
|Orientation=minus
|ReferenceAllele=A
|MissenseAllele=G
|GMAF=0.4302
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=FCGR2A
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 28.3 | 45.1 | 26.5
| HCB | 12.4 | 43.8 | 43.8
| JPT | 3.5 | 32.7 | 63.7
| YRI | 26.0 | 53.4 | 20.5
| ASW | 17.5 | 57.9 | 24.6
| CHB | 12.4 | 43.8 | 43.8
| CHD | 10.2 | 49.1 | 40.7
| GIH | 17.8 | 45.5 | 36.6
| LWK | 24.5 | 47.3 | 28.2
| MEX | 26.3 | 33.3 | 40.4
| MKK | 23.7 | 52.6 | 23.7
| TSI | 17.6 | 44.1 | 38.2
| HapMapRevision=28
}}
[[rs1801274]] is a SNP in the Fc fragment of IgG, low affinity IIa, receptor (CD32) [[FCGR2A]] gene. [[rs1801274]](C) encodes the arginine (R) allele, with the (T) allele encoding the variant histidine (H). The (H) isoform is considered high-binding to IgG2 and IgG3, while the (R) isoform is considered low-binding. This SNP is known in the literature by many names, including A519C and R131H. {{PMID|2527271}}

What's the importance of this? FcgR isoforms expressed on immune system cells 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 FCGR2A SNP, roughly divided by either disorder or treatment as follows:

* [[HIV]] to [[AIDS]], including susceptibility and progression
** In a study of HIV-infected men, those with a FCGR2a CC genotype progressed to a CD4+ cell count of <200/mm3 at a faster rate than individuals with either of the other genotypes (relative hazard = 1.6; p = 0.0001). However, the authors noted that the progression to [[AIDS]] was less impacted by this SNP, largely because TT homozygotes had an increased risk of pneumonia as an AIDS-defining illness. {{PMID|18025239}}

* [[Lymphoma]]
** A US study {{PMID|17018637}} of 1,172 lymphoma patients and 982 controls looked at 57 SNPs in 36 immune function genes. The AG and AA genotypes of [[rs1801274]] were associated with higher risk of follicular and small lymphocytic lymphomas: 1.26x (95% CI, 1.01-1.56) and 1.41x (95% CI, 1.10-1.81), respectively (P(trend) = 0.006).

* [[Malaria]]
** Based on a study of more than 1,800 individuals in India, [[rs1801274]](T;T) homozgyotes were significantly associated with protection from disease manifestation, with stronger association observed in the [[malaria]] non-endemic region. {{PMID|18194515|OA=1
}}

* [[Systemic lupus erythematosus]] (SLE)
** A study of 90 Japanese patients with SLE concluded that individuals with [[rs1801274]](C) alleles were at higher risk for the disease. {{PMID|11237133}}

Classifying the reports by immunotherapeutic treatment studied yields the following:

* Studies involving [[cetuximab]]:
** In a study of 39 patients with metastatic [[colorectal cancer]] treated with [[cetuximab]], the [[rs1801274]](T) (ie H) allele was associated with longer progression-free survival (PFS; p = 0.055), by perhaps 1-2 months. {{PMID|17704420}}

* Studies involving [[infliximab]]:
** A study of 91 patients with [[rheumatoid arthritis]] found that at week 30 of treatment with [[infliximab]], [[rs1801274]](C;C) homozygotes had a better ACR20 response (RR: 60% and HH-RH: 33.3%; p= 0.035). {{PMID|18930989}}

* Studies involving [[rituximab]]:
** In a study of 58 Croatian patients with [[diffuse large B-cell lymphoma]], [[rs1801274]] did not influence response, event-free or overall survival. {{PMID|17606457}}

* Studies involving 3F8, an anti-GD2 antibody:
** In a study of 136 patients with high risk [[neuroblastoma]] treated with the anti-GD2 antibody 3F8 plus GM-CSF immunotherapy, the [[rs1801274]](C;C)(ie R/R) genotype was correlated with progression-free survival for the entire cohort (p = .049) and for the subset of patients with no history of prior relapse (p = .023). {{PMID|16682723}}

{{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
}}
{{PMID Auto
|PMID=19915573
|Title=A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population
}}

{{omim
|desc=Fc FRAGMENT OF IgG, LOW AFFINITY IIa, RECEPTOR FOR; FCGR2A
|id=146790
|rsnum=1801274
}}

{{PMID Auto
|PMID=20149216
|Title=Fcgamma receptor polymorphisms and their association with periodontal disease: a meta-analysis
}}
{{PMID Auto
|PMID=20148910
|Title=Association of FcGRIIa with Graves' disease: a potential role for dysregulated autoantibody clearance in disease onset/progression
}}

{{PMID Auto
|PMID=20439102
|Title=Analysis of MIF, FCGR2A and FCGR3A gene polymorphisms with susceptibility to pulmonary tuberculosis in Moroccan population
}}
{{PMID Auto
|PMID=20691091
|Title=Survival dimensionality reduction (SDR): development and clinical application of an innovative approach to detect epistasis in presence of right-censored data
|OA=1
}}
{{PMID Auto
|PMID=21208440
|Title=Polymorphisms of CD16A and CD32 Fcgamma Receptors and Circulating Immunocomplexes in Meniere Disease: a case-control study
|OA=1
}}

{{omim
|id=266600
|rsnum=1801274
}}

{{PMID Auto GWAS
|PMID=21297633
|Trait=None
|Title=Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47
|RiskAllele=A
|Pval=2E-20
|OR=1.2100
|ORtxt=[1.16-1.26]
|OA=1
}}

{{PMID Auto
|PMID=21723269
|Title=Genetic profiling of GSTP1, DPYD, FCGR2A, FCGR3A and CCND1 genes in an Argentinian population
}}

{{PMID Auto
|PMID=22081228
|Title=Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease
}}

{{PMID Auto
|PMID=22446962
|Title=A genome-wide association study identifies three new risk loci for Kawasaki disease
}}

{{ClinVar
|rsid=1801274
|Reversed=1
|FwdREF=T
|FwdALT=C
|REF=A
|ALT=G
|RSPOS=161509955
|CHROM=1
|GMAF=0.4304
|dbSNPBuildID=89
|SSR=0
|SAO=1
|VP=0x050368000a1515051f130100
|GENEINFO=FCGR2A:2212
|GENE_NAME=FCGR2A
|GENE_ID=2212
|WGT=1
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000001.11:g.161509955A>G
|CLNORIGIN=1
|CLNSIG=255
|Tags=RV;PM;PMC;S3D;SLO;NSM;REF;OTH;ASP;VLD;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;MTP;OM
|CAF=0.5698; 0.4302
|CLNACC=RCV000015946.2; RCV000015947.2; RCV000054529.1
|CLNDBN=Lupus nephritis, susceptibility to; Pseudomonas aeruginosa, susceptibility to chronic infection by, in cystic fibrosis; Malaria, severe, susceptibility to
|CLNSRC=ClinVar; OMIM Allelic Variant
|CLNSRCID=NM_021642.3:c.497A>G; 146790.0001
|COMMON=1
|Disease=Lupus nephritis; Pseudomonas aeruginosa; Malaria
}}

{{PMID Auto
|PMID=15657875
|Title=Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus.
|OA=1
}}

{{PMID Auto
|PMID=16846490
|Title=Lemierre's syndrome and genetic polymorphisms: a case report.
|OA=1
}}

{{PMID Auto
|PMID=16893392
|Title=The FCGR2A--Arg131 variant is no major mortality factor in the elderly--evidence from a German centenarian study.
}}

{{PMID Auto
|PMID=17315188
|Title=Common variants in genes that mediate immunity and risk of multiple myeloma.
}}

{{PMID Auto
|PMID=17327408
|Title=Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival.
|OA=1
}}

{{PMID Auto
|PMID=17668374
|Title=Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants.
|OA=1
}}

{{PMID Auto
|PMID=18418394
|Title=Association study of IL2/IL21 and FcgRIIa: significant association with the IL2/IL21 region in Scandinavian coeliac disease families.
}}

{{PMID Auto
|PMID=18633131
|Title=Host immune gene polymorphisms in combination with clinical and demographic factors predict late survival in diffuse large B-cell lymphoma patients in the pre-rituximab era.
|OA=1
}}

{{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=18796628
|Title=Etiologic heterogeneity among non-Hodgkin lymphoma subtypes.
|OA=1
}}

{{PMID Auto
|PMID=18936436
|Title=Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.
|OA=1
}}

{{PMID Auto
|PMID=19066394
|Title=Organochlorine exposure, immune gene variation, and risk of non-Hodgkin lymphoma.
|OA=1
}}

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

{{PMID Auto
|PMID=19545442
|Title=Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa.
|OA=1
}}

{{PMID Auto
|PMID=19838195
|Title=A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus.
|OA=1
}}

{{PMID Auto
|PMID=20041166
|Title=Common genetic variation and the control of HIV-1 in humans.
|OA=1
}}

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

{{PMID Auto
|PMID=21317643
|Title=The Fcgamma receptor IIA-H/H131 genotype is associated with bacteremia in pneumococcal community-acquired pneumonia.
}}

{{PMID Auto
|PMID=21379322
|Title=Risk alleles for systemic lupus erythematosus in a large case-control collection and associations with clinical subphenotypes.
|OA=1
}}

{{PMID Auto
|PMID=21408207
|Title=Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production.
|OA=1
}}

{{PMID Auto
|PMID=21737555
|Title=Genetic variants associated with severe pneumonia in A/H1N1 influenza infection.
|OA=1
}}

{{PMID Auto
|PMID=21768177
|Title=Is FCGR2A a susceptibility gene to systemic lupus erythematosus in Chinese?
}}

{{PMID Auto
|PMID=21831733
|Title=Association of FCGR2A, JAK2 or HNF4A variants with ulcerative colitis in Koreans.
}}

{{PMID Auto
|PMID=22417159
|Title=DNA sequence variation and regulation of genes involved in pathogenesis of pulmonary tuberculosis.
}}

{{PMID Auto
|PMID=22484354
|Title=Calcineurin Inhibitor Treatment of Intravenous Immunoglobulin-Resistant Kawasaki Disease.
|OA=1
}}

{{PMID Auto
|PMID=22540264
|Title=The rs150311303 Polymorphism in FcgammaRIIa Enhances IgG Binding Capacity.
}}

{{GET Evidence
|gene=FCGR2A
|aa_change=His167Arg
|aa_change_short=H167R
|impact=not reviewed
|qualified_impact=Insufficiently evaluated not reviewed
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs1801274
|overall_frequency_n=5682
|overall_frequency_d=10758
|overall_frequency=0.528165
|n_genomes=3
|n_genomes_annotated=0
|n_haplomes=4
|n_articles=0
|n_articles_annotated=0
|nblosum100=1
|autoscore=0
|webscore=N
}}

{{PMID Auto
|PMID=22691414
|Title=Role of polymorphisms of toll-like receptor (TLR) 4, TLR9, toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and FCGR2A genes in malaria susceptibility and severity in Burundian children
|OA=1
}}

[[Malaria Complications]]

{{PMID Auto GWAS
  |PMID=23128233
  |Trait=Inflammatory bowel disease
  |Title=Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
  |RiskAllele=A
  |Pval=2E-38
  |OR=1.12
  |ORtxt=[1.092-1.157]
  |OA=1
}}

{{PMID Auto
|PMID=23498761
|Title=[Single nucleotide polymorphism of FCGR2A gene in Han Chinese children with Kawasaki disease]
}}

{{PMID Auto
|PMID=23456091
|Title=Combined analysis of genome-wide-linked susceptibility loci to Kawasaki disease in Han Chinese
}}

{{PMID Auto
|PMID=23906684
|Title=Genetic associations with coronary heart disease: Meta-analyses of 12 candidate genetic variants
}}

{{PMID Auto
|PMID=24225286
|Title=[Meta-analyses of the associations of genome-wide association study- linked gene loci with Kawasaki disease]
}}

{{PMID Auto
|PMID=24586589
|Title=Functional fcgamma receptor polymorphisms are associated with human allergy
|OA=1
}}

{{PMID Auto
|PMID=21780194
|Title=E-selectin rs5361 and FCGR2A rs1801274 variants were associated with increased risk of gastric cancer in a Chinese population.
}}

{{PMID Auto
|PMID=22922574
|Title=Fcgamma receptor polymorphisms do not predict response to intravenous immunoglobulin in myasthenia gravis.
}}

{{PMID Auto
|PMID=23459936
|Title=Exploring the genetic basis of chronic periodontitis: a genome-wide association study.
|OA=1
}}

{{PMID Auto
|PMID=23649770
|Title=Associations between FCGR2A rs1801274, FCGR3A rs396991, FCGR3B NA1/NA2 polymorphisms and periodontitis: a meta-analysis.
}}

{{PMID Auto
|PMID=24775607
|Title=Absence of association of FCGR2A gene polymorphism rs1801274 with Kawasaki disease in Greek patients
}}

{{PMID Auto
|PMID=25093412
|Title=A Genetic Variant rs1801274 in FCGR2A as a Potential Risk Marker for Kawasaki Disease: A Case-Control Study and Meta-Analysis
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}