{{Rsnum
|rsid=3087243
|Gene=CTLA4
|Chromosome=2
|position=203874196
|Orientation=plus
|GMAF=0.3242
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=CTLA4
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 20.4 | 51.3 | 28.3
| HCB | 2.9 | 32.8 | 64.2
| JPT | 7.1 | 42.5 | 50.4
| YRI | 2.0 | 28.6 | 69.4
| ASW | 5.3 | 36.8 | 57.9
| CHB | 2.9 | 32.8 | 64.2
| CHD | 6.4 | 34.9 | 58.7
| GIH | 40.6 | 48.5 | 10.9
| LWK | 0.0 | 26.4 | 73.6
| MEX | 17.2 | 50.0 | 32.8
| MKK | 3.8 | 20.5 | 75.6
| TSI | 31.4 | 46.1 | 22.5
| HapMapRevision=28
}}The [[rs3087243]] SNP is also known in the literature as the CT60 G>A or the +6230G>A polymorphism, and it is located in the [[CTLA4]] gene.

{{PMID|16352685}} In Asian (Japanese) populations, the presence of an [[rs3087243]](G) allele represents a 1.3 fold increased risk of autoimmune thyroid disease, and for those with autoimmune thyroid disease, a 1.5 fold increased risk of [[type-1 diabetes]]. However, in individuals without autoimmune thyroid disease, no association was seen between this SNP and type-1 diabetes. The authors speculate that earlier studies may have reported associations between this SNP and type-1 diabetes that were actually primarily based on the association with autoimmune thyroid disease.

This same SNP, [[rs3087243]], has also been implicated as a (minor) risk factor for developing [[rheumatoid arthritis]] (RA). A study of 2,000+ European RA patients led to a calculated odds ratio of 1.13 (CI: 1.03 - 1.24) for the [[rs3087243(G)]] risk allele. {{PMID|16380915|OA=1
}}

In a study of 395 Spanish patients with [[lupus]], [[rs3087243]](G) allele carriers were calculated to have an odds ratio of 1.71 (CI: 1.18-2.49, p=0.003, p(corr) = 0.006).{{PMID|15248219}}

In a different study involving recipients of liver transplants, although also with Spanish patients, the [[rs3087243]](G) allele was significantly associated with acute rejection (odds ratio 1.49, p(corr)=0.038). Patients who lacked this allele had the lowest risk of acute rejection development. Allograft survival data did not show statistical differences between genotypes.{{PMID|18047932}} 

{{PMID|18940880}} [[rs2292399]] and [[rs2903692]] both significantly associated with [[type 1 diabetes]] odds ratio 1.37 and 1.28. A joint analysis revealed that [[rs3087243]], [[rs2292399]], and [[rs2903692]], but not INS [[rs689]], were significant risk factors for the cooccurrence of AITD

{{PMID Auto
|PMID=19300490
|Title=An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans.
|OA=1
}}

{{PMID Auto GWAS
|PMID=18978792
|Trait=Type 1 diabetes
|Title=Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci
|RiskAllele=A
|Pval=8E-11
|OR=NR
|ORtxt=NR
|OA=1
}}

{{PMID Auto GWAS
|PMID=19430480
|Trait=Type 1 diabetes
|Title=Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes
|RiskAllele=
|Pval=1E-15
|OR=NR
|ORtxt=NR
|OA=1
}}
{{PMID Auto
|PMID=19506323
|Title=The Onset of Diabetes in Three out of Four Sisters: A Japanese Family with Type 1 Diabetes. A Case Report
}}

{{PMID Auto
|PMID=19404967
|Title=Confirmation of STAT4, IL2/IL21, and CTLA4 polymorphisms in rheumatoid arthritis
}}

{{omim
|id=123890
|desc=CYTOTOXIC T LYMPHOCYTE-ASSOCIATED 4; CTLA4
|rsnum=3087243
}}
{{PMID Auto
|PMID=19895365
|Title=Functional polymorphism in CTLA4 gene influences the response to therapy with inhaled corticosteroids in Slovenian children with atopic asthma
}}

{{PharmGKB
|RSID=rs3087243
|Name_s=
|Gene_s=CTLA4
|Feature=
|Evidence=PubMed ID:18978792; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. (Initial Sample Size: 3,561 cases, 4,646 controls; Replication Sample Size: 6,225 cases, 6,946 controls, 3,064 trios); (Region: 2q33.2; Reported Gene(s): CTLA4; Risk Allele: rs3087243-A); (p-value= 0.00000000008).This variant is associated with Type 1 diabetes.
|Drugs=
|Drug Classes=
|Diseases=Diabetes Mellitus; Diabetes Mellitus, Type 1
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740759
}}

{{PMID Auto
|PMID=19951419
|Title=Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis
|OA=1
}}

{{PMID Auto
|PMID=20537165
|Title=The CTLA4 variants may interact with the IL23R- and NOD2-conferred risk in development of Crohn's disease
|OA=1
}}
{{PMID Auto GWAS
|PMID=20453842
|Trait=Rheumatoid arthritis
|Title=Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk lock
|RiskAllele=G
|Pval=1E-8
|OR=1.15
|ORtxt=[1.10-1.20]
}}
{{PMID Auto
|PMID=20498205
|Title=Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers
|OA=1
}}
{{PMID Auto
|PMID=20825955
|Title=Clinical and genetic characteristics of patients with autoimmune thyroid disease with anti-islet autoimmunity
}}

{{omim
|id=123890
|rsnum=3087243
|variant=0002
}}

{{PMID Auto
|PMID=21637411
|Title=CTLA4CT60 gene polymorphism is not associated with differential susceptibility to pemphigus foliaceus
|OA=1
}}

{{PMID Auto
|PMID=21040781
|Title=CTLA-4 confers a risk of recurrent schizophrenia, major depressive disorder and bipolar disorder in the Chinese Han population
}}

{{PMID Auto GWAS
|PMID=21829393
|Trait=None
|Title=Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.
|RiskAllele=A
|Pval=2E-17
|OR=1.2000
|ORtxt=[NR]
|OA=1
}}

{{PMID Auto
|PMID=15452244
|Title=Cytotoxic T-lymphocyte antigen 4 gene and recovery from hepatitis B virus infection.
|OA=1
}}

{{PMID Auto
|PMID=17209142
|Title=Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes.
}}

{{PMID Auto
|PMID=17334650
|Title=A type 1 diabetes subgroup with a female bias is characterised by failure in tolerance to thyroid peroxidase at an early age and a strong association with the cytotoxic T-lymphocyte-associated antigen-4 gene.
|OA=1
}}

{{PMID Auto
|PMID=17554260
|Title=Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=17606874
|Title=Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=17666451
|Title=Associations between human leukocyte antigen, PTPN22, CTLA4 genotypes and rheumatoid arthritis phenotypes of autoantibody status, age at diagnosis and erosions in a large cohort study.
|OA=1
}}

{{PMID Auto
|PMID=17825114
|Title=Association of CTLA-4 gene polymorphisms with sporadic breast cancer in Chinese Han population.
|OA=1
}}

{{PMID Auto
|PMID=17940599
|Title=Assembly of inflammation-related genes for pathway-focused genetic analysis.
|OA=1
}}

{{PMID Auto
|PMID=18000051
|Title=Allelic variant in CTLA4 alters T cell phosphorylation patterns.
|OA=1
}}

{{PMID Auto
|PMID=18200060
|Title=PTPN22 is genetically associated with risk of generalized vitiligo, but CTLA4 is not.
}}

{{PMID Auto
|PMID=18252225
|Title=On the use of general control samples for genome-wide association studies: genetic matching highlights causal variants.
|OA=1
}}

{{PMID Auto
|PMID=18456185
|Title=Genetics and genomics of primary biliary cirrhosis.
|OA=1
}}

{{PMID Auto
|PMID=18462498
|Title=Genetic polymorphisms in PTPN22, PADI-4, and CTLA-4 and risk for rheumatoid arthritis in two longitudinal cohort studies: evidence of gene-environment interactions with heavy cigarette smoking.
|OA=1
}}

{{PMID Auto
|PMID=18466531
|Title=Case-control association analysis of rheumatoid arthritis with candidate genes using related cases.
|OA=1
}}

{{PMID Auto
|PMID=18528295
|Title=Influence of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) common polymorphisms on outcome in treatment of melanoma patients with CTLA-4 blockade.
|OA=1
}}

{{PMID Auto
|PMID=18556337
|Title=Impact of diabetes susceptibility loci on progression from pre-diabetes to diabetes in at-risk individuals of the diabetes prevention trial-type 1 (DPT-1).
|OA=1
}}

{{PMID Auto
|PMID=18576317
|Title=Lack of association of functional CTLA4 polymorphisms with juvenile idiopathic arthritis.
|OA=1
}}

{{PMID Auto
|PMID=18773895
|Title=The genetic basis of primary biliary cirrhosis: premises, not promises.
|OA=1
}}

{{PMID Auto
|PMID=18776148
|Title=Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis: from epidemiology to mechanisms.
|OA=1
}}

{{PMID Auto
|PMID=18778710
|Title=Primary biliary cirrhosis is associated with a genetic variant in the 3' flanking region of the CTLA4 gene.
|OA=1
}}

{{PMID Auto
|PMID=18794853
|Title=Common variants at CD40 and other loci confer risk of rheumatoid arthritis.
|OA=1
}}

{{PMID Auto
|PMID=18805939
|Title=Functional genetic polymorphisms and female reproductive disorders: part II--endometriosis.
|OA=1
}}

{{PMID Auto
|PMID=18853133
|Title=Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=19014504
|Title=Lack of association between sCTLA-4 levels in human plasma and common CTLA-4 polymorphisms.
|OA=1
}}

{{PMID Auto
|PMID=19073967
|Title=Shared and distinct genetic variants in type 1 diabetes and celiac disease.
|OA=1
}}

{{PMID Auto
|PMID=19141582
|Title=Autoimmune thyroiditis and diabetes: dissecting the joint genetic susceptibility in a large cohort of multiplex families.
|OA=1
}}

{{PMID Auto
|PMID=19147066
|Title=Genomic and proteomic analysis of allogeneic hematopoietic cell transplant outcome. Seeking greater understanding the pathogenesis of GVHD and mortality.
|OA=1
}}

{{PMID Auto
|PMID=19175525
|Title=CTLA4 and generalized vitiligo: two genetic association studies and a meta-analysis of published data.
|OA=1
}}

{{PMID Auto
|PMID=19359276
|Title=Identification of AF4/FMR2 family, member 3 (AFF3) as a novel rheumatoid arthritis susceptibility locus and confirmation of two further pan-autoimmune susceptibility genes.
|OA=1
}}

{{PMID Auto
|PMID=19609446
|Title=CTLA4 autoimmunity-associated genotype contributes to severe pulmonary tuberculosis in an African population.
|OA=1
}}

{{PMID Auto
|PMID=19622768
|Title=CTLA4 variants, UV-induced tolerance, and risk of non-melanoma skin cancer.
|OA=1
}}

{{PMID Auto
|PMID=19672595
|Title=Polymorphisms in the CD28/CTLA4/ICOS genes: role in malignant melanoma susceptibility and prognosis?
|OA=1
}}

{{PMID Auto
|PMID=19740340
|Title=The CTLA-4 gene polymorphisms are associated with CTLA-4 protein expression levels in multiple sclerosis patients and with susceptibility to disease.
|OA=1
}}

{{PMID Auto
|PMID=19956097
|Title=Remapping the type I diabetes association of the CTLA4 locus.
|OA=1
}}

{{PMID Auto
|PMID=19956101
|Title=Overview of the Rapid Response data.
|OA=1
}}

{{PMID Auto
|PMID=19956106
|Title=Analysis of 19 genes for association with type I diabetes in the Type I Diabetes Genetics Consortium families.
|OA=1
}}

{{PMID Auto
|PMID=20072139
|Title=Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis.
|OA=1
}}

{{PMID Auto
|PMID=20236493
|Title=The contribution of genetic variation and infection to the pathogenesis of ANCA-associated systemic vasculitis.
|OA=1
}}

{{PMID Auto
|PMID=20300120
|Title=HLA and CTLA4 polymorphisms may confer a synergistic risk in the susceptibility to Graves' disease.
}}

{{PMID Auto
|PMID=20352109
|Title=Association of the CTLA4 gene with Graves' disease in the Chinese Han population.
|OA=1
}}

{{PMID Auto
|PMID=20439292
|Title=Genetic variants in the prediction of rheumatoid arthritis.
}}

{{PMID Auto
|PMID=20444755
|Title=Investigation of rheumatoid arthritis susceptibility genes identifies association of AFF3 and CD226 variants with response to anti-tumour necrosis factor treatment.
|OA=1
}}

{{PMID Auto
|PMID=20491567
|Title=CTLA4 CT60 single-nucleotide polymorphism is associated with Slovenian inflammatory bowel disease patients and regulates expression of CTLA4 isoforms.
}}

{{PMID Auto
|PMID=20557968
|Title=Association analysis of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with primary biliary cirrhosis in Japanese patients.
}}

{{PMID Auto
|PMID=20610662
|Title=Association of single nucleotide polymorphisms in cytotoxic T-lymphocyte antigen 4 and susceptibility to autoimmune type 1 diabetes in Tunisians.
|OA=1
}}

{{PMID Auto
|PMID=21383967
|Title=Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.
|OA=1
}}

{{PMID Auto
|PMID=21669243
|Title=CTLA-4, CD28, and ICOS gene polymorphism associations with non-small-cell lung cancer.
}}

{{PMID Auto
|PMID=22414241
|Title=Cytotoxic T-lymphocyte associated antigen-4 gene polymorphisms and primary biliary cirrhosis: A systematic review.
}}

{{PMID Auto
|PMID=22418270
|Title=Polymorphisms in cytotoxic T lymphocyte associated antigen-4 influence the rate of acute rejection after renal transplantation in 167 Chinese recipients.
}}

{{PMID Auto
|PMID=22511809
|Title=Association of variants in HLA-DQA1-DQB1, PTPN22, INS, and CTLA4 with GAD autoantibodies and insulin secretion in nondiabetic adults of the Botnia Prospective Study.
}}

{{GET Evidence
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs3087243
|overall_frequency_n=51
|overall_frequency_d=128
|overall_frequency=0.398438
|n_genomes=27
|n_genomes_annotated=0
|n_haplomes=35
|n_articles=0
|n_articles_annotated=0
|in_gwas=Y
|in_pharmgkb=Y
|autoscore=2
|webscore=N
}}

{{PMID Auto
|PMID=23432218
|Title=Association between cytotoxic T-lymphocyte antigen 4 gene polymorphisms and primary biliary cirrhosis in Chinese population: data from a multicenter study
}}

{{PMID Auto
|PMID=23480667
|Title=Cytotoxic T-Lymphocyte Antigen-4 Genetic Variants and Risk of Ewing's Sarcoma
}}

{{PMID Auto
|PMID=23567921
|Title=Cytotoxic T-lymphocyte antigen 4 (CTLA4) +49AG and CT60 gene polymorphisms in Alopecia Areata: a case-control association study in the Italian population
}}

{{PMID Auto
|PMID=23597029
|Title=The associations between the polymorphisms in the CTLA-4 gene and the risk of Graves' disease in the Chinese population
|OA=1
}}

{{PMID Auto
|PMID=23703660
|Title=The -319C/+49G/CT60G Haplotype of CTLA-4 Gene Confers Susceptibility to Rheumatoid Arthritis in Mexican Population
}}

{{PMID Auto
|PMID=24015180
|Title=CTLA4 Gene Polymorphisms Influence the Incidence of Infection after Renal Transplantation in Chinese Recipients
|OA=1
}}

{{PMID Auto
|PMID=24270470
|Title=Influence of cytotoxic T lymphocyte-associated antigen 4 polymorphisms on the outcomes of hepatitis B virus infection
}}

{{PMID Auto
|PMID=24313821
|Title=Association of CTLA-4 Gene Polymorphism with End-Stage Renal Disease and Renal Allograft Outcome
}}

{{PMID Auto
|PMID=22328738
|Title=Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort.
|OA=1
}}

{{PMID Auto
|PMID=22891215
|Title=Evidence of gene-gene interaction and age-at-diagnosis effects in type 1 diabetes.
|OA=1
}}

{{PMID Auto GWAS
  |PMID=24390342
  |Trait=Rheumatoid arthritis
  |Title=Genetics of rheumatoid arthritis contributes to biology and drug discovery.
  |RiskAllele=G
  |Pval=3E-25
  |OR=1.14
  |ORtxt=[1.11-1.17]
  }}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6}}
{{on chip | HumanOmni1Quad}}