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From SNPedia

Geno Mag Summary
(A;A) 1.5 increased risk for auto-immune diseases
(A;G) 1.5 increased risk for auto-immune diseases
(G;G) 1 Normal risk for autoimmune diseases
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
1000 genomesrs3087243
23andMe allrs3087243
SNP Nexus

GWAS Ctlgrs3087243
Max Magnitude1.5
? (A;A) (A;G) (G;G) 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 16380915OA-icon.png]

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 19300490OA-icon.png] An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans.

GWAS snp
PMID [PMID 18978792OA-icon.png]
Trait Type 1 diabetes
Title Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci
Risk Allele A
P-val 8E-11
Odds Ratio NR NR
GWAS snp
PMID [PMID 19430480OA-icon.png]
Trait Type 1 diabetes
Title Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes
Risk Allele
P-val 1E-15
Odds Ratio NR NR

[PMID 19506323] The Onset of Diabetes in Three out of Four Sisters: A Japanese Family with Type 1 Diabetes. A Case Report

[PMID 19404967] Confirmation of STAT4, IL2/IL21, and CTLA4 polymorphisms in rheumatoid arthritis


[PMID 19895365] Functional polymorphism in CTLA4 gene influences the response to therapy with inhaled corticosteroids in Slovenian children with atopic asthma

[PMID 19951419OA-icon.png] Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis

[PMID 20537165OA-icon.png] The CTLA4 variants may interact with the IL23R- and NOD2-conferred risk in development of Crohn's disease

GWAS snp
PMID [PMID 20453842OA-icon.png]
Trait Rheumatoid arthritis
Title Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk lock
Risk Allele G
P-val 1E-8
Odds Ratio 1.15 [1.10-1.20]

[PMID 20498205OA-icon.png] Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers

[PMID 20825955] Clinical and genetic characteristics of patients with autoimmune thyroid disease with anti-islet autoimmunity

[PMID 21637411OA-icon.png] CTLA4CT60 gene polymorphism is not associated with differential susceptibility to pemphigus foliaceus

[PMID 21040781] CTLA-4 confers a risk of recurrent schizophrenia, major depressive disorder and bipolar disorder in the Chinese Han population

GWAS snp
PMID [PMID 21829393OA-icon.png]
Title Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.
Risk Allele A
P-val 2E-17
Odds Ratio 1.2000 [NR]

[PMID 15452244OA-icon.png] Cytotoxic T-lymphocyte antigen 4 gene and recovery from hepatitis B virus infection.

[PMID 17209142] Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes.

[PMID 17334650OA-icon.png] 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.

[PMID 17554260OA-icon.png] Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes.

[PMID 17606874OA-icon.png] Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes.

[PMID 17666451OA-icon.png] 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.

[PMID 17825114OA-icon.png] Association of CTLA-4 gene polymorphisms with sporadic breast cancer in Chinese Han population.

[PMID 17940599OA-icon.png] Assembly of inflammation-related genes for pathway-focused genetic analysis.

[PMID 18000051OA-icon.png] Allelic variant in CTLA4 alters T cell phosphorylation patterns.

[PMID 18200060] PTPN22 is genetically associated with risk of generalized vitiligo, but CTLA4 is not.

[PMID 18252225OA-icon.png] On the use of general control samples for genome-wide association studies: genetic matching highlights causal variants.

[PMID 18456185OA-icon.png] Genetics and genomics of primary biliary cirrhosis.

[PMID 18462498OA-icon.png] 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.

[PMID 18466531OA-icon.png] Case-control association analysis of rheumatoid arthritis with candidate genes using related cases.

[PMID 18528295OA-icon.png] Influence of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) common polymorphisms on outcome in treatment of melanoma patients with CTLA-4 blockade.

[PMID 18556337OA-icon.png] 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).

[PMID 18576317OA-icon.png] Lack of association of functional CTLA4 polymorphisms with juvenile idiopathic arthritis.

[PMID 18773895OA-icon.png] The genetic basis of primary biliary cirrhosis: premises, not promises.

[PMID 18776148OA-icon.png] Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis: from epidemiology to mechanisms.

[PMID 18778710OA-icon.png] Primary biliary cirrhosis is associated with a genetic variant in the 3' flanking region of the CTLA4 gene.

[PMID 18794853OA-icon.png] Common variants at CD40 and other loci confer risk of rheumatoid arthritis.

[PMID 18805939OA-icon.png] Functional genetic polymorphisms and female reproductive disorders: part II--endometriosis.

[PMID 18853133OA-icon.png] Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes.

[PMID 19014504OA-icon.png] Lack of association between sCTLA-4 levels in human plasma and common CTLA-4 polymorphisms.

[PMID 19073967OA-icon.png] Shared and distinct genetic variants in type 1 diabetes and celiac disease.

[PMID 19141582OA-icon.png] Autoimmune thyroiditis and diabetes: dissecting the joint genetic susceptibility in a large cohort of multiplex families.

[PMID 19147066OA-icon.png] Genomic and proteomic analysis of allogeneic hematopoietic cell transplant outcome. Seeking greater understanding the pathogenesis of GVHD and mortality.

[PMID 19175525OA-icon.png] CTLA4 and generalized vitiligo: two genetic association studies and a meta-analysis of published data.

[PMID 19359276OA-icon.png] Identification of AF4/FMR2 family, member 3 (AFF3) as a novel rheumatoid arthritis susceptibility locus and confirmation of two further pan-autoimmune susceptibility genes.

[PMID 19609446OA-icon.png] CTLA4 autoimmunity-associated genotype contributes to severe pulmonary tuberculosis in an African population.

[PMID 19622768OA-icon.png] CTLA4 variants, UV-induced tolerance, and risk of non-melanoma skin cancer.

[PMID 19672595OA-icon.png] Polymorphisms in the CD28/CTLA4/ICOS genes: role in malignant melanoma susceptibility and prognosis?

[PMID 19740340OA-icon.png] The CTLA-4 gene polymorphisms are associated with CTLA-4 protein expression levels in multiple sclerosis patients and with susceptibility to disease.

[PMID 19956097OA-icon.png] Remapping the type I diabetes association of the CTLA4 locus.

[PMID 19956101OA-icon.png] Overview of the Rapid Response data.

[PMID 19956106OA-icon.png] Analysis of 19 genes for association with type I diabetes in the Type I Diabetes Genetics Consortium families.

[PMID 20072139OA-icon.png] Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis.

[PMID 20236493OA-icon.png] The contribution of genetic variation and infection to the pathogenesis of ANCA-associated systemic vasculitis.

[PMID 20300120] HLA and CTLA4 polymorphisms may confer a synergistic risk in the susceptibility to Graves' disease.

[PMID 20352109OA-icon.png] Association of the CTLA4 gene with Graves' disease in the Chinese Han population.

[PMID 20439292] Genetic variants in the prediction of rheumatoid arthritis.

[PMID 20444755OA-icon.png] Investigation of rheumatoid arthritis susceptibility genes identifies association of AFF3 and CD226 variants with response to anti-tumour necrosis factor treatment.

[PMID 20491567] CTLA4 CT60 single-nucleotide polymorphism is associated with Slovenian inflammatory bowel disease patients and regulates expression of CTLA4 isoforms.

[PMID 20557968] Association analysis of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with primary biliary cirrhosis in Japanese patients.

[PMID 20610662OA-icon.png] Association of single nucleotide polymorphisms in cytotoxic T-lymphocyte antigen 4 and susceptibility to autoimmune type 1 diabetes in Tunisians.

[PMID 21383967OA-icon.png] Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.

[PMID 21669243] CTLA-4, CD28, and ICOS gene polymorphism associations with non-small-cell lung cancer.

[PMID 22414241] Cytotoxic T-lymphocyte associated antigen-4 gene polymorphisms and primary biliary cirrhosis: A systematic review.

[PMID 22418270] Polymorphisms in cytotoxic T lymphocyte associated antigen-4 influence the rate of acute rejection after renal transplantation in 167 Chinese recipients.

[PMID 22511809] 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
overall_frequency 0.398438

[PMID 23432218] Association between cytotoxic T-lymphocyte antigen 4 gene polymorphisms and primary biliary cirrhosis in Chinese population: data from a multicenter study

[PMID 23480667] Cytotoxic T-Lymphocyte Antigen-4 Genetic Variants and Risk of Ewing's Sarcoma

[PMID 23567921] Cytotoxic T-lymphocyte antigen 4 (CTLA4) +49AG and CT60 gene polymorphisms in Alopecia Areata: a case-control association study in the Italian population

[PMID 23597029OA-icon.png] The associations between the polymorphisms in the CTLA-4 gene and the risk of Graves' disease in the Chinese population

[PMID 23703660] The -319C/+49G/CT60G Haplotype of CTLA-4 Gene Confers Susceptibility to Rheumatoid Arthritis in Mexican Population

[PMID 24015180OA-icon.png] CTLA4 Gene Polymorphisms Influence the Incidence of Infection after Renal Transplantation in Chinese Recipients

[PMID 24270470] Influence of cytotoxic T lymphocyte-associated antigen 4 polymorphisms on the outcomes of hepatitis B virus infection

[PMID 24313821] Association of CTLA-4 Gene Polymorphism with End-Stage Renal Disease and Renal Allograft Outcome

[PMID 22328738OA-icon.png] Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort.

[PMID 22891215OA-icon.png] Evidence of gene-gene interaction and age-at-diagnosis effects in type 1 diabetes.

GWAS snp
PMID [PMID 24390342OA-icon.png]
Trait Rheumatoid arthritis
Title Genetics of rheumatoid arthritis contributes to biology and drug discovery.
Risk Allele G
P-val 3E-25
Odds Ratio 1.14 [1.11-1.17]

[PMID 25940108OA-icon.png] A CT60G>A polymorphism in the CTLA-4 gene of the recipient may confer susceptibility to acute graft versus host disease after allogeneic hematopoietic stem cell transplantation

[PMID 26079279] HCV F protein amplifies the predictions of IL-28B and CTLA-4 polymorphisms about the susceptibility and outcomes of HCV infection in Southeast China

[PMID 26405547OA-icon.png] Association of the CTLA4 gene CT60/rs3087243 single-nucleotide polymorphisms with Graves' disease

[PMID 26403483] CTLA-4 and CD28 genes' polymorphisms and renal cell carcinoma susceptibility in the Polish population - a prospective study

[PMID 26656450] Variation in the CTLA4 3'UTR has phenotypic consequences for autoreactive T cells and associates with genetic risk for type 1 diabetes.