{{Rsnum
|rsid=231775
|Gene=CTLA4
|Chromosome=2
|position=203867991
|Orientation=plus
|ReferenceAllele=A
|MissenseAllele=G
|GMAF=0.4522
|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 | 36.3 | 49.6 | 14.2
| HCB | 8.8 | 44.1 | 47.1
| JPT | 13.4 | 49.1 | 37.5
| YRI | 40.1 | 46.3 | 13.6
| ASW | 33.3 | 54.4 | 12.3
| CHB | 8.8 | 44.1 | 47.1
| CHD | 11.9 | 43.1 | 45.0
| GIH | 49.5 | 40.6 | 9.9
| LWK | 30.0 | 46.4 | 23.6
| MEX | 37.9 | 51.7 | 10.3
| MKK | 26.3 | 48.7 | 25.0
| TSI | 52.5 | 41.6 | 5.9
| HapMapRevision=28
}}

[[rs231775]], also known as +49A/G, is a SNP in the [[CTLA4]] gene. which is linked to [[Hashimoto thyroiditis]]

{{omim
|desc=HASHIMOTO THYROIDITIS, SUSCEPTIBILITY TO
|id=123890
|rsnum=231775
|variant=0001
}}

In a meta-analysis of [[CTLA4]] gene SNPs, [[rs231775]] was most associated with [[vitiligo]]; however, the association seems to hold only in the subgroup of patients with other autoimmune diseases.{{PMID|19175525|OA=1
}}

{{PMID|18059468}} [[rs231775]] (CTLA4_+49_G/A P=0.0219) and [[rs733618]] (CTLA4_-1722_T/C P=0.0096) susceptibility to [[Graves' disease]]

{{PMID|18076363}} associated with the development of placental abruption and [[preeclampsia]], with women having the G allele being at risk

{{PMID|19490216}} [[rs231775]] was not associated with type-1 diabetes in a study of 207 Portuguese patients.

{{PMID Auto
|PMID=19438904
|Title=Clinical associations of the genetic variants of CTLA-4, Tg, TSHR, PTPN22, PTPN12 and FCRL3 in patients with Graves' disease
}}

{{PMID Auto
|PMID=19778566
|Title=+49G&gt;A polymorphism in the CTLA-4 gene increases susceptibility to HBV-related HCC in male Chinese population
}}
{{PMID Auto
|PMID=19780033
|Title=Association of a functional polymorphism of PTPN22 encoding a lymphoid protein phosphatase in bilateral Meniere's disease
}}

{{PharmGKB
|RSID=rs231775
|Name_s=CTLA4:A49G
|Gene_s=CTLA4
|Feature=
|Evidence=PubMed ID:18485327
|Annotation=This SNP affects risk for Autoimmune Thyroid Disorder (AITD). The G allele is generally thought to be the risk-conferring allele, but this study found that which allele confers risk actually depends upon the genetic background.
|Drugs=
|Drug Classes=
|Diseases=Autoimmune Diseases; Autoimmune Thyroid Disease; Graves Disease; Thyroiditis, Autoimmune
|Curation Level=Curated
|PharmGKB Accession ID=PA162372686
}}

{{PMID Auto
|PMID=19386687
|Title=CTLA4 gene polymorphisms are associated with chronic bronchitis
}}

{{PMID Auto
|PMID=20538028
|Title=CTLA-4 gene polymorphism +49 A/G is contributed to genetic susceptibility to two infection related cancers: hepatocellular carcinoma and cervical cancer
}}
{{PMID Auto
|PMID=20940051
|Title=Polymorphisms of the CTLA4 gene and kidney transplant rejection in Korean patients
}}

{{PharmGKB
|RSID=rs231775
|Name_s=
|Gene_s=CTLA4
|Feature=
|Evidence=PubMed ID:18021981
|Annotation=A study in 82 renal transplant recipients suggests that appearance of an adenosine allele(A) in this SNP of the CTLA-4 gene may be a permissive element for cyclosporine-induced gingival overgrowth.
|Drugs=cyclosporine
|Drug Classes=
|Diseases=Gingival Overgrowth
|Curation Level=Curated
|PharmGKB Accession ID=PA162263537
}}

{{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
|PMID=21513760
|Title=Association of CTLA4 gene polymorphisms with lymphatic filariasis in an East Malaysian population
}}

{{PMID Auto
|PMID=22011251
|Title=Cytotoxic T-Lymphocyte Antigen-4 +49G/A Polymorphism and Susceptibility to Pancreatic Cancer
}}

{{PMID Auto
|PMID=22718509
|Title=Association between CTLA-4 exon-1 +49A/G polymorphism and systemic lupus erythematosus: an updated analysis
}}

{{ClinVar
|rsid=231775
|Reversed=0
|FwdREF=A
|FwdALT=G
|REF=A
|ALT=G
|RSPOS=204732714
|CHROM=2
|GMAF=0.4519
|dbSNPBuildID=79
|SSR=0
|SAO=0
|VP=0x05016800000015051f110100
|GENEINFO=CTLA4:1493
|GENE_NAME=CTLA4
|GENE_ID=1493
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000002.11:g.204732714A>G
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=123890.0001
|CLNSIG=255
|CLNCUI=C1857845
|CLNDBN=Hashimoto thyroiditis, susceptibility to; Thyroid-associated orbitopathy, susceptibility to; Systemic lupus erythematosus, susceptibility to; Diabetes mellitus, insulin-dependent, susceptibility to; Celiac disease 3
|Disease=Hashimoto thyroiditis; Thyroid-associated orbitopathy; Systemic lupus erythematosus; Diabetes mellitus; Celiac disease 3
|CLNACC=RCV000018423.1; RCV000018424.1; RCV000018425.1; RCV000018426.1; RCV000018427.1
|Tags=PM;PMC;SLO;VLD;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;OM
|CAF=0.5478; 0.4522
|CLNDSDB=MedGen:OMIM
|CLNDSDBID=C1857845:609755
|COMMON=1
}}

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

{{PMID Auto
|PMID=15726497
|Title=Gene-environment interaction effects on the development of immune responses in the 1st year of life.
|OA=1
}}

{{PMID Auto
|PMID=16380915
|Title=Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4.
|OA=1
}}

{{PMID Auto
|PMID=16449530
|Title=Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma.
|OA=1
}}

{{PMID Auto
|PMID=16872485
|Title=Three allele combinations associated with multiple sclerosis.
|OA=1
}}

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

{{PMID Auto
|PMID=17683561
|Title=The TCF7L2 locus and type 1 diabetes.
|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=18200060
|Title=PTPN22 is genetically associated with risk of generalized vitiligo, but CTLA4 is not.
}}

{{PMID Auto
|PMID=18456185
|Title=Genetics and genomics of primary biliary cirrhosis.
|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=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=18687755
|Title=Genetic variants in T helper cell type 1, 2 and 3 pathways and gastric cancer risk in a Polish population.
|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=18805939
|Title=Functional genetic polymorphisms and female reproductive disorders: part II--endometriosis.
|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=19066394
|Title=Organochlorine exposure, immune gene variation, and risk of non-Hodgkin lymphoma.
|OA=1
}}

{{PMID Auto
|PMID=19131662
|Title=A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.
|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=19173720
|Title=Low frequency of CD4+CD25+ Treg in SLE patients: a heritable trait associated with CTLA4 and TGFbeta gene variants.
|OA=1
}}

{{PMID Auto
|PMID=19180256
|Title=Genotype analysis of polymorphisms in autoimmune susceptibility genes, CTLA-4 and PTPN22, in an acute anterior uveitis cohort.
|OA=1
}}

{{PMID Auto
|PMID=19188433
|Title=Do non-HLA genes influence development of persistent islet autoimmunity and type 1 diabetes in children with high-risk HLA-DR,DQ genotypes?
|OA=1
}}

{{PMID Auto
|PMID=19263529
|Title=Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach.
|OA=1
}}

{{PMID Auto
|PMID=19300490
|Title=An African ancestry-specific allele of CTLA4 confers protection against rheumatoid arthritis in African Americans.
|OA=1
}}

{{PMID Auto
|PMID=19330901
|Title=Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.
|OA=1
}}

{{PMID Auto
|PMID=19379518
|Title=Development of a fingerprinting panel using medically relevant polymorphisms.
|OA=1
}}

{{PMID Auto
|PMID=19559392
|Title=A candidate gene association study of 77 polymorphisms in migraine.
|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=19956109
|Title=The Type I Diabetes Genetics Consortium 'Rapid Response' family-based candidate gene study: strategy, genes selection, and main outcome.
|OA=1
}}

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

{{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=20537165
|Title=The CTLA4 variants may interact with the IL23R- and NOD2-conferred risk in development of Crohn's disease.
|OA=1
}}

{{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=20565774
|Title=Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.
|OA=1
}}

{{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=20732370
|Title=CTLA4 and CD86 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease.
}}

{{PMID Auto
|PMID=21085187
|Title=Comprehensive association analysis of candidate genes for generalized vitiligo supports XBP1, FOXP3, and TSLP.
|OA=1
}}

{{PMID Auto
|PMID=21453059
|Title=Cytotoxic T-lymphocyte antigen-4 +49G/A polymorphism is associated with increased risk of osteosarcoma.
}}

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

{{PMID Auto
|PMID=21952918
|Title=Evidence for gene-gene epistatic interactions among susceptibility loci for systemic lupus erythematosus.
|OA=1
}}

{{PMID Auto
|PMID=22076708
|Title=Validation of genetic sequence variants as prognostic factors in early-stage head and neck squamous cell cancer survival.
}}

{{PMID Auto
|PMID=22288822
|Title=A pilot study on cytotoxic T lymphocyte-4 gene polymorphisms in urinary schistosomiasis.
|OA=1
}}

{{PMID Auto
|PMID=22376040
|Title=Gene-gene interactions between candidate gene polymorphisms are associated with total IgE levels in Korean children with asthma.
}}

{{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=23018253
|Title=The impact of rs231775 (+49AG) CTLA4 gene polymorphism on transplanted kidney function
}}

{{GET Evidence
|gene=CTLA4
|aa_change=Thr17Ala
|aa_change_short=T17A
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs231775
|overall_frequency_n=3986
|overall_frequency_d=10758
|overall_frequency=0.370515
|n_genomes=30
|n_genomes_annotated=0
|n_haplomes=40
|n_articles=1
|n_articles_annotated=1
|in_pharmgkb=Y
|pph2_score=0.001
|nblosum100=1
|autoscore=1
|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=23661460
|Title=CTLA-4 and CD86 genetic variants and haplotypes in patients with rheumatoid arthritis in southeastern China
}}

{{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=23830732
|Title=CTLA-4 gene polymorphism at position +49 A&gt;G in exon 1: a risk factor for cervical cancer in Indian women
}}

{{PMID Auto
|PMID=23944755
|Title=The impact of CTLA4 and PTPN22 genes polymorphisms on long-term renal allograft function and transplant outcomes
}}

{{PMID Auto
|PMID=23961418
|Title=Association of the HLA locus and TNF with type I autoimmune hepatitis susceptibility in New Zealand Caucasians
|OA=1
}}

{{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=24298899
|Title=Investigation of CTLA-4 and CD86 gene polymorphisms in a group of Iranian patients with brucellosis infection
}}

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

{{PMID Auto
|PMID=24385694
|Title=Effect of cytotoxic T-lymphocyte antigen-4, TNF-alpha polymorphisms on osteosarcoma: evidences from a meta-analysis
|OA=1
}}

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

{{PMID Auto
|PMID=22905924
|Title=Cytotoxic T-lymphocyte antigen-4 polymorphisms and susceptibility to Ewing's sarcoma.
}}

{{PMID Auto
|PMID=23010350
|Title=Lack of association between CTLA-4 +49A/G and -318C/T polymorphisms and Behcet's disease risk: a meta-analysis.
}}

{{PMID Auto
|PMID=23133602
|Title=Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.
|OA=1
}}

{{PMID Auto
|PMID=23261825
|Title=Association between cytotoxic T lymphocyte antigen-4 polymorphism and type 1 diabetes: a meta-analysis.
}}

{{PMID Auto
|PMID=25005490
|Title=The association of PTPN22 rs2476601 polymorphism and CTLA-4 rs231775 polymorphism with LADA risks: a systematic review and meta-analysis
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}