rs1801274
| Orientation | minus |
| Stabilized | minus |
| Geno | Mag | Summary |
|---|---|---|
| (C;C) | 1 | normal risk for cancer progression |
| (C;T) | 1.5 | complex; generally greater risk for cancer progression |
| (T;T) | 1.5 | complex; generally greater risk for cancer progression |
| Reference | GRCh38 38.1/141 |
| Chromosome | 1 |
| Position | 161509955 |
| Gene | FCGR2A |
| is a | snp |
| is | mentioned by |
| dbSNP | rs1801274 |
| dbSNP (classic) | rs1801274 |
| ClinGen | rs1801274 |
| ebi | rs1801274 |
| HLI | rs1801274 |
| Exac | rs1801274 |
| Gnomad | rs1801274 |
| Varsome | rs1801274 |
| LitVar | rs1801274 |
| Map | rs1801274 |
| PheGenI | rs1801274 |
| Biobank | rs1801274 |
| 1000 genomes | rs1801274 |
| hgdp | rs1801274 |
| ensembl | rs1801274 |
| geneview | rs1801274 |
| scholar | rs1801274 |
| rs1801274 | |
| pharmgkb | rs1801274 |
| gwascentral | rs1801274 |
| openSNP | rs1801274 |
| 23andMe | rs1801274 |
| SNPshot | rs1801274 |
| SNPdbe | rs1801274 |
| MSV3d | rs1801274 |
| GWAS Ctlg | rs1801274 |
| GMAF | 0.4302 |
| Max Magnitude | 1.5 |
| ? | (C;C) (C;T) (T;T) | 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 H131R. [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).
- Hemophilia A
- In a case-control study of 85 individuals a more than 3-fold increased risk of inhibitor development was found compared to patients with the RR genotype[PMID 24916518]
- 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
]
- 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
- 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 19140833] Linkage and association study of FcgammaR polymorphisms in celiac disease
[PMID 19640933] FCGR2B gene polymorphism rather than FCGR2A, FCGR3A and FCGR3B is associated with anti-GBM disease in Chinese
[PMID 19915573] A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population
[PMID 20149216] Fcgamma receptor polymorphisms and their association with periodontal disease: a meta-analysis
[PMID 20148910] Association of FcGRIIa with Graves' disease: a potential role for dysregulated autoantibody clearance in disease onset/progression
[PMID 20439102] Analysis of MIF, FCGR2A and FCGR3A gene polymorphisms with susceptibility to pulmonary tuberculosis in Moroccan population
[PMID 20691091
] Survival dimensionality reduction (SDR): development and clinical application of an innovative approach to detect epistasis in presence of right-censored data
[PMID 21208440] Polymorphisms of CD16A and CD32 Fcgamma Receptors and Circulating Immunocomplexes in Meniere Disease: a case-control study
| GWAS snp | |
|---|---|
| PMID | [PMID 21297633]
|
| Trait | |
| Title | Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47 |
| Risk Allele | A |
| P-val | 2E-20 |
| Odds Ratio | 1.2100 [1.16-1.26] |
[PMID 21723269] Genetic profiling of GSTP1, DPYD, FCGR2A, FCGR3A and CCND1 genes in an Argentinian population
[PMID 22081228] Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease
[PMID 22446962] A genome-wide association study identifies three new risk loci for Kawasaki disease
| ClinVar | |
|---|---|
| Risk | Rs1801274(C;C) |
| Alt | Rs1801274(C;C) |
| Reference | Rs1801274(T;T) |
| Significance | Other |
| Disease | Lupus nephritis Pseudomonas aeruginosa Malaria trastuzumab response - Efficacy not specified |
| Variation | info |
| Gene | FCGR2A |
| CLNDBN | Lupus nephritis, susceptibility to Pseudomonas aeruginosa, susceptibility to chronic infection by, in cystic fibrosis Malaria, severe, susceptibility to trastuzumab response - Efficacy not specified |
| Reversed | 1 |
| HGVS | NC_000001.10:g.161479745A>G |
| CLNSRC | OMIM Allelic Variant PharmGKB Clinical Annotation |
| CLNACC | RCV000015946.3, RCV000015947.3, RCV000054529.2, RCV000211160.1, RCV000454909.1, |
[PMID 15657875] Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus.
[PMID 16846490] Lemierre's syndrome and genetic polymorphisms: a case report.
[PMID 16893392] The FCGR2A--Arg131 variant is no major mortality factor in the elderly--evidence from a German centenarian study.
[PMID 17315188] Common variants in genes that mediate immunity and risk of multiple myeloma.
[PMID 17327408] Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival.
[PMID 17668374] Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants.
[PMID 18418394] Association study of IL2/IL21 and FcgRIIa: significant association with the IL2/IL21 region in Scandinavian coeliac disease families.
[PMID 18633131] 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.
[PMID 18759263] Features associated with, and the impact of, hemolytic anemia in patients with systemic lupus erythematosus: LX, results from a multiethnic cohort.
[PMID 18796628] Etiologic heterogeneity among non-Hodgkin lymphoma subtypes.
[PMID 18936436] Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.
[PMID 19066394] Organochlorine exposure, immune gene variation, and risk of non-Hodgkin lymphoma.
[PMID 19421223] Fcgamma receptors: structure, function and role as genetic risk factors in SLE.
[PMID 19545442] Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa.
[PMID 19838195] A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus.
[PMID 20041166] Common genetic variation and the control of HIV-1 in humans.
[PMID 20508037] Copy number, linkage disequilibrium and disease association in the FCGR locus.
[PMID 21317643] The Fcgamma receptor IIA-H/H131 genotype is associated with bacteremia in pneumococcal community-acquired pneumonia.
[PMID 21379322] Risk alleles for systemic lupus erythematosus in a large case-control collection and associations with clinical subphenotypes.
[PMID 21408207] Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production.
[PMID 21737555] Genetic variants associated with severe pneumonia in A/H1N1 influenza infection.
[PMID 21768177] Is FCGR2A a susceptibility gene to systemic lupus erythematosus in Chinese?
[PMID 21831733] Association of FCGR2A, JAK2 or HNF4A variants with ulcerative colitis in Koreans.
[PMID 22417159] DNA sequence variation and regulation of genes involved in pathogenesis of pulmonary tuberculosis.
[PMID 22484354] Calcineurin Inhibitor Treatment of Intravenous Immunoglobulin-Resistant Kawasaki Disease.
[PMID 22540264] The rs150311303 Polymorphism in FcgammaRIIa Enhances IgG Binding Capacity.
[PMID 22691414] 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
| GWAS snp | |
|---|---|
| PMID | [PMID 23128233]
|
| Trait | Inflammatory bowel disease |
| Title | Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. |
| Risk Allele | A |
| P-val | 2E-38 |
| Odds Ratio | 1.12 [1.092-1.157] |
[PMID 23498761] [Single nucleotide polymorphism of FCGR2A gene in Han Chinese children with Kawasaki disease]
[PMID 23456091] Combined analysis of genome-wide-linked susceptibility loci to Kawasaki disease in Han Chinese
[PMID 23906684] Genetic associations with coronary heart disease: Meta-analyses of 12 candidate genetic variants
[PMID 24225286] [Meta-analyses of the associations of genome-wide association study- linked gene loci with Kawasaki disease]
[PMID 24586589] Functional fcgamma receptor polymorphisms are associated with human allergy
[PMID 21780194] E-selectin rs5361 and FCGR2A rs1801274 variants were associated with increased risk of gastric cancer in a Chinese population.
[PMID 22922574] Fcgamma receptor polymorphisms do not predict response to intravenous immunoglobulin in myasthenia gravis.
[PMID 23459936] Exploring the genetic basis of chronic periodontitis: a genome-wide association study.
[PMID 23649770] Associations between FCGR2A rs1801274, FCGR3A rs396991, FCGR3B NA1/NA2 polymorphisms and periodontitis: a meta-analysis.
[PMID 24775607] Absence of association of FCGR2A gene polymorphism rs1801274 with Kawasaki disease in Greek patients
[PMID 25093412] A Genetic Variant rs1801274 in FCGR2A as a Potential Risk Marker for Kawasaki Disease: A Case-Control Study and Meta-Analysis
| GWAS snp | |
|---|---|
| PMID | [PMID 24871463]
|
| Trait | Systemic lupus erythematosus |
| Title | GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region. |
| Risk Allele | |
| P-val | 9E-6 |
| Odds Ratio | NR NR |
[PMID 25811666] Novel association of FCGR2A polymorphism with age-related macular degeneration (AMD) and development of a novel CFH real-time genotyping method
[PMID 26398853] Identification of Ten Additional Susceptibility Loci for Ulcerative Colitis Through Immunochip Analysis in Koreans
[PMID 27729837] Recapitulation of Candidate Systemic Lupus Erythematosus-Associated Variants in Koreans.
[PMID 29130827] Association of Single-Nucleotide Polymorphisms in Immune-Related Genes with Development of Dengue Hemorrhagic Fever in a Mexican Population.
[PMID 30260678] A Case-Control Study on Association of Ulcerative Colitis with FCGR2A Gene Polymorphisms in Chinese Patients.
[PMID 32235430] A Comparative Analysis of CD32A and CD16A Polymorphisms in Relation to Autoimmune Responses in Pemphigus Diseases and Subepithelial Autoimmune Blistering Disorders.
