rs3087243

G= better response to inhaled corticosteroids in patients with asthma [CTLA4 gene. [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, , 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 (G) risk allele. [lupus, (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).[type 1 diabetes odds ratio 1.37 and 1.28. A joint analysis revealed that , , and , but not INS , were significant risk factors for the cooccurrence of AITD [PMID 19300490] An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans. [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 19951419] Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis [PMID 20537165] The CTLA4 variants may interact with the IL23R- and NOD2-conferred risk in development of Crohn’s disease [PMID 20498205] 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 21637411] 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 [PMID 15452244] 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 17334650] 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 17554260] Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. [PMID 17606874] Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. [PMID 17666451] 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 17825114] Association of CTLA-4 gene polymorphisms with sporadic breast cancer in Chinese Han population. [PMID 17940599] Assembly of inflammation-related genes for pathway-focused genetic analysis. [PMID 18000051] 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 18252225] On the use of general control samples for genome-wide association studies: genetic matching highlights causal variants. [PMID 18456185] Genetics and genomics of primary biliary cirrhosis. [PMID 18462498] 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 18466531] Case-control association analysis of rheumatoid arthritis with candidate genes using related cases. [PMID 18528295] Influence of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) common polymorphisms on outcome in treatment of melanoma patients with CTLA-4 blockade. [PMID 18556337] 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 18576317] Lack of association of functional CTLA4 polymorphisms with juvenile idiopathic arthritis. [PMID 18773895] The genetic basis of primary biliary cirrhosis: premises, not promises. [PMID 18776148] Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis: from epidemiology to mechanisms. [PMID 18778710] Primary biliary cirrhosis is associated with a genetic variant in the 3′ flanking region of the CTLA4 gene. [PMID 18794853] Common variants at CD40 and other loci confer risk of rheumatoid arthritis. [PMID 18805939] Functional genetic polymorphisms and female reproductive disorders: part II–endometriosis. [PMID 18853133] Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes. [PMID 19014504] Lack of association between sCTLA-4 levels in human plasma and common CTLA-4 polymorphisms. [PMID 19073967] Shared and distinct genetic variants in type 1 diabetes and celiac disease. [PMID 19141582] Autoimmune thyroiditis and diabetes: dissecting the joint genetic susceptibility in a large cohort of multiplex families. [PMID 19147066] Genomic and proteomic analysis of allogeneic hematopoietic cell transplant outcome. Seeking greater understanding the pathogenesis of GVHD and mortality. [PMID 19175525] CTLA4 and generalized vitiligo: two genetic association studies and a meta-analysis of published data. [PMID 19359276] 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 19609446] CTLA4 autoimmunity-associated genotype contributes to severe pulmonary tuberculosis in an African population. [PMID 19622768] CTLA4 variants, UV-induced tolerance, and risk of non-melanoma skin cancer. [PMID 19672595] Polymorphisms in the CD28/CTLA4/ICOS genes: role in malignant melanoma susceptibility and prognosis? [PMID 19740340] The CTLA-4 gene polymorphisms are associated with CTLA-4 protein expression levels in multiple sclerosis patients and with susceptibility to disease. [PMID 19956097] Remapping the type I diabetes association of the CTLA4 locus. [PMID 19956101] Overview of the Rapid Response data. [PMID 19956106] Analysis of 19 genes for association with type I diabetes in the Type I Diabetes Genetics Consortium families. [PMID 20072139] Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis. [PMID 20236493] 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 20352109] Association of the CTLA4 gene with Graves’ disease in the Chinese Han population. [PMID 20439292] Genetic variants in the prediction of rheumatoid arthritis. [PMID 20444755] 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 20610662] Association of single nucleotide polymorphisms in cytotoxic T-lymphocyte antigen 4 and susceptibility to autoimmune type 1 diabetes in Tunisians. [PMID 21383967] 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.       [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 23597029] 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 24015180] 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 22328738] Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort. [PMID 22891215] Evidence of gene-gene interaction and age-at-diagnosis effects in type 1 diabetes. [PMID 25940108] 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 26405547] Association of the CTLA4 gene CT60/ 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.

G= better response to inhaled corticosteroids in patients with asthma [R].

In Asian (Japanese) populations, the presence of an (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 R.

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 (G) risk allele. [R]

In a study of 395 Spanish patients with lupus, (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).[R]

In a different study involving recipients of liver transplants, the (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.[R] [R]

Significantly associated with type 1 diabetes odds ratio 1.37 and 1.28 [R].