Gene Symbol: CTLA 4
Description: cytotoxic T-lymphocyte associated protein 4
Alias: ALPS5, CD152, CELIAC3, CTLA-4, GRD4, GSE, IDDM12, cytotoxic T-lymphocyte protein 4, CD152 isoform, celiac disease 3, cytotoxic T lymphocyte associated antigen 4 short spliced form, cytotoxic T-lymphocyte-associated serine esterase-4, insulin-dependent diabetes mellitus 12, ligand and transmembrane spliced cytotoxic T lymphocyte associated antigen 4
Species: human
Products:     CTLA 4

Top Publications

  1. Khaghanzadeh N, Erfani N, Ghayumi M, Ghaderi A. CTLA4 gene variations and haplotypes in patients with lung cancer. Cancer Genet Cytogenet. 2010;196:171-4 pubmed publisher
    ..We also could not find significant association between CTLA4 variants and any defined lung tumor type. These six single-nucleotide polymorphisms in CTLA4 were not associated with susceptibility to lung cancer in Iranian population. ..
  2. Liu J, Zhang H. -1722T/C polymorphism (rs733618) of CTLA-4 significantly associated with systemic lupus erythematosus (SLE): a comprehensive meta-analysis. Hum Immunol. 2013;74:341-7 pubmed publisher
    ..946, 95% CI: (0.707-1.267), p = 0.711; random: OR: 0.973, 95% CI: (0.606-1.560), p = 0.908}. These results suggest that there is evidence of association between the CLTA-4 and SLE, especially -1722T/C polymorphism (rs733618). ..
  3. Rahimifar S, Erfani N, Sarraf Z, Ghaderi A. ctla-4 gene variations may influence cervical cancer susceptibility. Gynecol Oncol. 2010;119:136-9 pubmed publisher
    ..Investigation of ctla-4 gene variants in other ethnic populations will consolidate the findings of this study. ..
  4. Kämmerer P, Toyoshima T, Schöder F, Kämmerer P, Kuhr K, Brieger J, et al. Association of T-cell regulatory gene polymorphisms with oral squamous cell carcinoma. Oral Oncol. 2010;46:543-8 pubmed publisher
    ..Therefore, they might be future targets for a primary prophylaxis or an individualised therapy. ..
  5. Zheng Y, Manzotti C, Burke F, Dussably L, Qureshi O, Walker L, et al. Acquisition of suppressive function by activated human CD4+ CD25- T cells is associated with the expression of CTLA-4 not FoxP3. J Immunol. 2008;181:1683-91 pubmed
    ..These data suggest that the acquisition of suppressive behavior by activated CD4(+)CD25(-) T cells requires the expression of CTLA-4, a feature that appears to be facilitated by, but is not dependent on, expression of FoxP3. ..
  6. Berce V, Potocnik U. Functional polymorphism in CTLA4 gene influences the response to therapy with inhaled corticosteroids in Slovenian children with atopic asthma. Biomarkers. 2010;15:158-66 pubmed publisher
    ..SNP CT60 in the CTLA4 gene plays only a minor role in genetic susceptibility to childhood asthma in the Caucasian population. ..
  7. Hu L, Liu J, Chen X, Zhang Y, Liu L, Zhu J, et al. CTLA-4 gene polymorphism +49 A/G contributes to genetic susceptibility to two infection-related cancers-hepatocellular carcinoma and cervical cancer. Hum Immunol. 2010;71:888-91 pubmed publisher
    ..43-fold (95% CI = 0.94-2.17) for HCC, and 1.66-fold (95% CI = 1.13-2.44) for cervical cancer. Taken together, the results suggest that CTLA4 rs231775 may serve as a common cancer susceptibility marker. ..
  8. Chen S, Deng F, Jiang F, Liu J, Meng W. [Correlation between CTLA-4 gene polymorphism and systemic lupus erythematosus: a meta-analysis]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2012;28:1320-3 pubmed
    ..This meta-analysis supports that the CTLA-4 1722T/C and -318T/C polymorphisms are associated with SLE susceptibility, especially in Asian population. ..
  9. Zaletel K, Krhin B, Gaberscek S, Bicek A, Pajic T, Hojker S. Association of CT60 cytotoxic T lymphocyte antigen-4 gene polymorphism with thyroid autoantibody production in patients with Hashimoto's and postpartum thyroiditis. Clin Exp Immunol. 2010;161:41-7 pubmed publisher
    ..In PPT, the genotype also seems to influence thyroid function, as patients with the polymorphous allele are more prone to develop hypothyroid form of PPT. ..

More Information


  1. Karabon L, Kosmaczewska A, Bilinska M, Pawlak E, Ciszak L, Jedynak A, et al. The CTLA-4 gene polymorphisms are associated with CTLA-4 protein expression levels in multiple sclerosis patients and with susceptibility to disease. Immunology. 2009;128:e787-96 pubmed publisher
    ..e. CT60A and Jo31T) may lead to inadequate down-regulation of ongoing T-cell responses in these patients and, as a consequence, earlier progression of disease from the RR form to the SP form. ..
  2. Benhatchi K, Jochmanová I, Habalova V, Wagnerová H, Lazúrová I. CTLA4 exon1 A49G polymorphism in Slovak patients with rheumatoid arthritis and Hashimoto thyroiditis-results and the review of the literature. Clin Rheumatol. 2011;30:1319-24 pubmed publisher
    ..08-3.81). The frequency of GG genotype of CTLA4 A49G gene polymorphism in Slovak patients with RA is not significantly higher in comparison to control group. However, carriers of GG genotype with RA may be susceptible to develop HT. ..
  3. Karimi M, Motazedian M, Abedi F, Yaghobi R, Geramizadeh B, Nikeghbalian S. Association of genetic variation in co-stimulatory molecule genes with outcome of liver transplant in Iranian patients. Gene. 2012;504:127-32 pubmed publisher
    ..The present results demonstrate that potentially functional genetic variation in T-cell co-stimulatory molecules including ICOS, CTLA4 and CD28 can influence liver transplant outcome. ..
  4. Wang W, Wang J, Song H, Liu J, Song B, Cao X. Cytotoxic T-lymphocyte antigen-4 +49G/A polymorphism is associated with increased risk of osteosarcoma. Genet Test Mol Biomarkers. 2011;15:503-6 pubmed publisher
    ..27, p=0.010, and OR 1.41, p=0.015). Our data suggest that the +49G/A polymorphism of CTLA-4 gene is associated with increased susceptibility to osteosarcoma. ..
  5. Qi P, Ruan C, Wang H, Zhou F, Xu X, Gu X, et al. CTLA-4 +49A>G polymorphism is associated with the risk but not with the progression of colorectal cancer in Chinese. Int J Colorectal Dis. 2010;25:39-45 pubmed publisher
    ..Our results suggested that CTLA-4 +49A>G polymorphism was associated with an increased risk of colorectal cancer, but this polymorphism did not play an important role in the progression of CRC in Chinese. ..
  6. Muñoz Valle J, Valle Y, Padilla Gutiérrez J, Parra Rojas I, Rangel Villalobos H, Vazquez Del Mercado M, et al. The +49A>G CTLA-4 polymorphism is associated with rheumatoid arthritis in Mexican population. Clin Chim Acta. 2010;411:725-8 pubmed publisher
    ..There was no evidence of an association between SNP genotypes and the clinical characteristics of rheumatoid arthritis. The +49A>G CTLA-4 polymorphism is a genetic marker of susceptibility for RA in western Mexican population. ..
  7. Antczak A, Pastuszak Lewandoska D, Górski P, Domańska D, Migdalska Sek M, Czarnecka K, et al. Ctla-4 expression and polymorphisms in lung tissue of patients with diagnosed non-small-cell lung cancer. Biomed Res Int. 2013;2013:576486 pubmed publisher
    ..The shift from one genotype in the blood to another in the tumor may confirm the complexity of gene functionality in cancer tissue. ..
  8. Chen Z, Fei M, Fu D, Zhang L, Ma Y, Wang Y, et al. Association between cytotoxic T lymphocyte antigen-4 polymorphism and type 1 diabetes: a meta-analysis. Gene. 2013;516:263-70 pubmed publisher
    ..This meta-analysis demonstrated that the G allele of rs231775 of CTLA-4 is a risk factor associated with increased T1D susceptibility. ..
  9. Ohmann E, Brooks M, Webber S, Girnita D, Ferrell R, Burckart G, et al. Association of genetic polymorphisms and risk of late post-transplantation infection in pediatric heart recipients. J Heart Lung Transplant. 2010;29:1342-51 pubmed publisher
    ..A weaker association was also found between late viral infection and GP of CTLA4, a regulator of T-cell activation. This represents progress toward understanding the clinical and genetic risk factors of outcomes after transplantation. ..
  10. Xiao M, Qi F, Chen X, Luo Z, Zhang L, Zheng C, et al. Functional polymorphism of cytotoxic T-lymphocyte antigen 4 and nasopharyngeal carcinoma susceptibility in a Chinese population. Int J Immunogenet. 2010;37:27-32 pubmed publisher
    Cytotoxic T-lymphocyte antigen 4 (CTLA-4; CD152) is a secondary receptor of B7 (CD80 and CD86) and shares homology with the CD28 receptor...
  11. Karabon L, Pawlak E, Tomkiewicz A, Jedynak A, Passowicz Muszyńska E, Zajda K, et al. CTLA-4, CD28, and ICOS gene polymorphism associations with non-small-cell lung cancer. Hum Immunol. 2011;72:947-54 pubmed publisher
    ..1554+4GT(8_15)[>10] was associated with a decreased overall survival rate. In conclusion, the constellation of specific alleles in CTLA-4, CD28, and ICOS genes contributes to the susceptibility and clinical course of NSCLC. ..
  12. Gu X, Qi P, Zhou F, Ji Q, Wang H, Dou T, et al. +49G > A polymorphism in the cytotoxic T-lymphocyte antigen-4 gene increases susceptibility to hepatitis B-related hepatocellular carcinoma in a male Chinese population. Hum Immunol. 2010;71:83-7 pubmed publisher
    ..31, 95% CI 1.03-1.66). These results suggested that the A/A genotype and A allele of rs231775 increased the risk of developing HBV-related HCC in a male Chinese population. ..
  13. Erfani N, Haghshenas M, Hoseini M, Hashemi S, Khademi B, Ghaderi A. Strong association of CTLA-4 variation (CT60A/G) and CTLA-4 haplotypes with predisposition of Iranians to head and neck cancer. Iran J Immunol. 2012;9:188-98 pubmed
    ..Our results suggest that CT60 A allele, as well as ACA and GTG haplotypes in CTLA-4 gene may have protective roles against HN cancer in Iranian population, while ACG, GTA and specially GCA haplotypes may render susceptibility. ..
  14. Benmansour J, Stayoussef M, Al Jenaidi F, Rajab M, Rayana C, Said H, et al. Association of single nucleotide polymorphisms in cytotoxic T-lymphocyte antigen 4 and susceptibility to autoimmune type 1 diabetes in Tunisians. Clin Vaccine Immunol. 2010;17:1473-7 pubmed publisher
    ..Our results indicate that CTLA-4 gene variants are associated with increased T1D susceptibility in Tunisian patients, further supporting a central role for altered T-cell costimulation in T1D pathogenesis. ..
  15. Daroszewski J, Pawlak E, Karabon L, Frydecka I, Jonkisz A, Slowik M, et al. Soluble CTLA-4 receptor an immunological marker of Graves' disease and severity of ophthalmopathy is associated with CTLA-4 Jo31 and CT60 gene polymorphisms. Eur J Endocrinol. 2009;161:787-93 pubmed publisher
    ..03). It was shown for the first time that increased serum concentration of sCTLA-4 correlate with the severity of GO. Genetic variation in the CTLA-4 gene region in GD patients at least partially determines the level of sCTLA-4. ..
  16. Ise W, Kohyama M, Nutsch K, Lee H, Suri A, Unanue E, et al. CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cell-extrinsic mechanisms. Nat Immunol. 2010;11:129-35 pubmed publisher
    ..Our results demonstrate that both cell-intrinsic and non-cell-autonomous actions of CTLA-4 operate to maintain T cell tolerance to a self antigen. ..
  17. Chua K, Puah S, Chew C, Tan S, Lian L. Study of the CTLA-4 gene polymorphisms in systemic lupus erythematosus (SLE) samples from Malaysia. Ann Hum Biol. 2010;37:274-80 pubmed publisher
    ..Hence, we propose that the CTLA-4 gene does not play a major role in the genetic susceptibility to the development of SLE in the Malaysian population. ..
  18. Jung M, Yu J, Shin C, Suh B, Yang S, Lee B. Association of cytotoxic T lymphocyte antigen-4 gene polymorphisms and HLA class II alleles with the development of type 1 diabetes in Korean children and adolescents. J Korean Med Sci. 2009;24:1004-9 pubmed publisher
    ..However, a CTLA4-mediated susceptibility effect on the development of T1D might be significant in children and adolescents that do not have susceptible HLA class II alleles. ..
  19. Tang S, Tang H, Zhang Q, Wang C, Wang Y, Peng W. Association of cytotoxic T-lymphocyte associated antigen 4 gene polymorphism with type 1 diabetes mellitus: a meta-analysis. Gene. 2012;508:165-87 pubmed publisher
    ..In conclusion, our results suggest that CTLA-4 polymorphism contributes to the susceptibility of T1DM. ..
  20. Wang X, Fan Z, Anton D, Vollenhoven A, Ni Z, Chen X, et al. CTLA4 is expressed on mature dendritic cells derived from human monocytes and influences their maturation and antigen presentation. BMC Immunol. 2011;12:21 pubmed publisher
    ..CTLA4-expressing DCs may represent a group of regulatory DCs. Because of its wide distribution on different cell types, CTLA4 may play a general role in regulating immune responses. ..
  21. Rocha M, Santos L, Bagatin E, Cohen Tervaert J, Damoiseaux J, Lido A, et al. Genetic polymorphisms and surface expression of CTLA-4 and PD-1 on T cells of silica-exposed workers. Int J Hyg Environ Health. 2012;215:562-9 pubmed publisher
    ..Since CTLA-4 [CD152] and PD-1 [CD279] are important for the maintenance of peripheral tolerance by regulating T cell responsiveness, ..
  22. Sun T, Hu Z, Shen H, Lin D. Genetic polymorphisms in cytotoxic T-lymphocyte antigen 4 and cancer: the dialectical nature of subtle human immune dysregulation. Cancer Res. 2009;69:6011-4 pubmed publisher
    ..The requisites of CTLA-4 polymorphisms for susceptibility to cancer and response to targeted therapy are discussed in this review. ..
  23. Joshita S, Umemura T, Yoshizawa K, Katsuyama Y, Tanaka E, Nakamura M, et al. Association analysis of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with primary biliary cirrhosis in Japanese patients. J Hepatol. 2010;53:537-41 pubmed publisher
    ..The connection between genetic variants and the function of the CTLA4 gene remains to be addressed in future investigations. ..
  24. Bouwhuis M, Gast A, Figl A, Eggermont A, Hemminki K, Schadendorf D, et al. Polymorphisms in the CD28/CTLA4/ICOS genes: role in malignant melanoma susceptibility and prognosis?. Cancer Immunol Immunother. 2010;59:303-12 pubmed publisher
  25. Si X, Zhang X, Luo Y, Tang W. Association between the CTLA-4 +49A/G polymorphism and type 1 diabetes: a meta-analysis. Genet Test Mol Biomarkers. 2012;16:1336-42 pubmed publisher
    ..Otherwise, we found that the studies of Africans are rare. More studies in Africans are needed especially. ..
  26. Qureshi O, Zheng Y, Nakamura K, Attridge K, Manzotti C, Schmidt E, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011;332:600-3 pubmed publisher
  27. Jiang L, Luo R, Zhang W, Wang L, Wang F, Cheng Y. [Single nucleotide polymorphisms of CTLA4 gene and their association with human cervical cancer]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2011;28:313-7 pubmed publisher
    ..SNPs in the promoter region of (CTLA4) gene might increase the susceptibility to cervical cancer by increasing (CTLA4) gene expression. ..
  28. Liu Y, He Z, Feng D, Shi G, Gao R, Wu X, et al. Cytotoxic T-lymphocyte antigen-4 polymorphisms and susceptibility to osteosarcoma. DNA Cell Biol. 2011;30:1051-5 pubmed publisher
    ..23-2.95, p?=?0.007; OR 1.32, 95% CI 1.03-1.69, p?=?0.029, and OR?=?1.47, 95% CI 1.03-2.09, p?=?0.033, respectively). The CTLA-4 +49G/A polymorphism and GTAG haplotype are associated with increased risk of osteosarcoma. ..
  29. Lee Y, Song G. CTLA-4 polymorphisms and susceptibility to Behcet's disease: a meta-analysis. Mol Biol Rep. 2012;39:9041-5 pubmed publisher
    ..No association was found between BD and the CTLA-4 -318 C/T or CT60 A/G polymorphisms. This meta-analysis showed that no association was found between CTLA-4 +49 A/G, -318 C/T or CT60 A/G polymorphisms and BD. ..
  30. Plant D, Flynn E, Mbarek H, Dieude P, Cornelis F, Arlestig L, et al. Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers. Ann Rheum Dis. 2010;69:1548-53 pubmed publisher
    ..Data from this study increased the significance for association with RA and nine markers. In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained. ..
  31. Mosaad Y, Elsharkawy A, El Deek B. Association of CTLA-4 (+49A/G) gene polymorphism with type 1 diabetes mellitus in Egyptian children. Immunol Invest. 2012;41:28-37 pubmed publisher
    ..The CTLA-4 +49 GG homozygous genotype is associated with T1D in Egyptian children especially with younger age of onset and in younger patients, and not associated with grades of diabetic control or diabetic complication. ..
  32. Cheng X, Ning T, Xu C, Li Y, Zhu B, Hou F, et al. Haplotype analysis of CTLA4 gene and risk of esophageal squamous cell carcinoma in Anyang area of China. Hepatogastroenterology. 2011;58:432-7 pubmed
    ..413, 95%CI=0.251-0.680, p=0.001). Our research confirmed that CTLA4 genetic variation was related to ESCC in the Anyang area and GAA haplotype was the protective factor of ESCC. ..
  33. Song B, Liu Y, Liu J, Song X, Wang Z, Wang M, et al. CTLA-4 +49A>G polymorphism is associated with advanced non-small cell lung cancer prognosis. Respiration. 2011;82:439-44 pubmed publisher
    ..Our data suggest that the polymorphism of CTLA-4 +49A>G is a prognostic predictor for advanced NSCLC. ..
  34. Li X, Zhang C, Zhang J, Zhang Y, Wu Z, Yang L, et al. Polymorphisms in the CTLA-4 gene and rheumatoid arthritis susceptibility: a meta-analysis. J Clin Immunol. 2012;32:530-9 pubmed publisher
    ..This meta-analysis suggested that the +49A/G and CT60 polymorphisms in the CTLA-4 gene may be risk factors for RA. ..
  35. Kimkong I, Nakkuntod J, Sae Ngow S, Snabboon T, Avihingsanon Y, Hirankarn N. Association between CTLA-4 polymorphisms and the susceptibility to systemic lupus erythematosus and Graves' disease in Thai population. Asian Pac J Allergy Immunol. 2011;29:229-35 pubmed
    ..We found no association between two functional polymorphisms (+49A/G and CT60A/G) of the CTLA-4 gene and susceptibility to SLE and GD. However, the association study utilizing a larger sample size should be performed to confirm this. ..
  36. Karabon L, Pawlak Adamska E, Tomkiewicz A, Jedynak A, Kielbinski M, Woszczyk D, et al. Variations in suppressor molecule ctla-4 gene are related to susceptibility to multiple myeloma in a polish population. Pathol Oncol Res. 2012;18:219-26 pubmed publisher
    ..79, 95%CI: 2.08-6.89, p?=?0.00001). These findings indicate that genetic variations in the CTLA-4 gene play role in susceptibility to multiple myeloma and warrant further investigation through replication studies. ..
  37. Li D, Zhang Q, Xu F, Fu Z, Yuan W, Li D, et al. Association of CTLA-4 gene polymorphisms with sporadic breast cancer risk and clinical features in Han women of northeast China. Mol Cell Biochem. 2012;364:283-90 pubmed publisher
    ..These results indicate that some SNPs in the CTLA-4 gene may affect the risk of breast cancer and show that some SNPs are associated with breast cancer characteristics in Han women in northeastern China. ..
  38. Zhang Y, Xu W, Duan Z, Liu S, Pan H, Ye D. Lack of association between CTLA-4 +49A/G and -318C/T polymorphisms and Behçet's disease risk: a meta-analysis. Clin Exp Rheumatol. 2012;30:S46-50 pubmed
    ..Further confirmations in large and well-designed studies including other CTLA-4 gene polymorphisms are needed. ..
  39. Mao H, Zhang L, Yang Y, Zuo W, Bi Y, Gao W, et al. New insights of CTLA-4 into its biological function in breast cancer. Curr Cancer Drug Targets. 2010;10:728-36 pubmed
  40. Kusztal M, Kościelska Kasprzak K, Drulis Fajdasz D, Magott Procelewska M, Patrzałek D, Janczak D, et al. The influence of CTLA-4 gene polymorphism on long-term kidney allograft function in Caucasian recipients. Transpl Immunol. 2010;23:121-4 pubmed publisher
    The aim of the study was to examine whether CTLA-4 (CD152) and CD28 gene polymorphisms affect the outcome of kidney transplantation (KTx)...
  41. Ivansson E, Juko Pecirep I, Gyllensten U. Interaction of immunological genes on chromosome 2q33 and IFNG in susceptibility to cervical cancer. Gynecol Oncol. 2010;116:544-8 pubmed publisher
    ..The opposite associations in the two populations could then be explained by differences in linkage disequilibrium and population structure. ..
  42. Vogt B, Warncke M, Micheel B, Sheriff A. Lentiviral gene transfer of CTLA4 generates B cells with reduced costimulatory properties. Autoimmunity. 2009;42:380-2 pubmed
    ..We show that B cells with reduced B7 expression reduce the antigen (Ag) specific TC proliferation in vitro. B cells expressing an ER-directed CTLA4 may reduce Ag-specific immune responses. ..
  43. Sellami M, Bani M, Torjemane L, Kaabi H, Ladeb S, Ben Othmane T, et al. Effect of donor CTLA-4 alleles and haplotypes on graft-versus-host disease occurrence in Tunisian patients receiving a human leukocyte antigen-identical sibling hematopoietic stem cell transplant. Hum Immunol. 2011;72:139-43 pubmed publisher
    ..We suppose that donor T cells expressing this haplotype in a homozygous state have higher proliferation than those expressing other haplotypes, especially after recognition of the recipient's minor histocompatibility antigens. ..
  44. Lee Y, Bae S, Choi S, Ji J, Song G. Association between the CTLA-4 +49 A/G polymorphism and susceptibility to rheumatoid arthritis: a meta-analysis. Mol Biol Rep. 2012;39:5599-605 pubmed publisher
    ..This meta-analysis demonstrates that the CTLA-4 +49 A/G polymorphism confers susceptibility to RA in Asians, but not in Caucasians. ..
  45. Chen R, Han Z, Li J, Shi Y, Zhou X, Wang J, et al. Cytotoxic T-lymphocyte antigen 4 gene +49A/G polymorphism significantly associated with susceptibility to primary biliary cirrhosis: a meta-analysis. J Dig Dis. 2011;12:428-35 pubmed publisher
    ..However, larger studies with participants of varying ethnicity and stratified by clinical and laboratory characteristics are needed to validate our findings. ..
  46. Zhai J, Zou L, Zhang Z, Fan W, Wang H, Liu T, et al. CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis. Mol Biol Rep. 2013;40:5213-23 pubmed publisher
    ..99, P = 0.04 for G vs. A) in Asian population.In summary, this meta-analysis demonstrates that the CTLA-4 promoter +49A/G and promoter -1722C/T polymorphism may confer susceptibility to SLE, especially in Asian-derived population. ..
  47. Wang J, Shi Y, Yue H, Chun W, Zou L. CTLA-4 exon 1 +49A/G polymorphism is associated with renal involvement in pediatric Henoch-Schönlein purpura. Pediatr Nephrol. 2012;27:2059-2064 pubmed publisher
    ..Our findings suggest that the CTLA-4 +49 GG genotype and G allele may contribute to increased risk for the development of renal damage in HSP patients. ..
  48. Hou R, Cao B, Chen Z, Li Y, Ning T, Li C, et al. Association of cytotoxic T lymphocyte-associated antigen-4 gene haplotype with the susceptibility to gastric cancer. Mol Biol Rep. 2010;37:515-20 pubmed publisher
    ..00, P < 0.001; OR = 1.62, P = 0.043, respectively). Our findings implied the genetic variations within CTLA-4 gene would be a critical risk factor to the susceptibility of gastric cancer. ..
  49. Plagnol V, Howson J, Smyth D, Walker N, Hafler J, Wallace C, et al. Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. PLoS Genet. 2011;7:e1002216 pubmed publisher
    ..Analysis of the TPOA-associated loci in 2,477 cases with Graves' disease identified two new AITD loci (BACH2 and UBASH3A). ..
  50. Korolija M, Renar I, Hadzija M, Medvidović E, Pavkovic P, Jokic M, et al. Association of PTPN22 C1858T and CTLA-4 A49G polymorphisms with Type 1 Diabetes in Croatians. Diabetes Res Clin Pract. 2009;86:e54-7 pubmed publisher
    ..0001). This is therefore the first evidence that analyzed gene variants contribute to T1D pathogenesis in Croatian population. ..
  51. Piccioli P, Balbi G, Serra M, Morabito A, Lamparelli T, Gobbi M, et al. CTLA-4 +49A>G polymorphism of recipients of HLA-matched sibling allogeneic stem cell transplantation is associated with survival and relapse incidence. Ann Hematol. 2010;89:613-8 pubmed publisher
  52. Pincerati M, Dalla Costa R, Pavoni D, Petzl Erler M. Genetic polymorphisms of the T-cell coreceptors CD28 and CTLA-4 in Afro- and Euro-Brazilians. Int J Immunogenet. 2010;37:253-61 pubmed publisher
    ..We conclude that disease association studies and functional studies addressing the possible consequences of polymorphisms of the 2q33 genomic region should consider haplotypic data besides analysis of individual polymorphisms. ..
  53. Bharti V, Mohanti B, Das S. Functional genetic variants of CTLA-4 and risk of tobacco-related oral carcinoma in high-risk North Indian population. Hum Immunol. 2013;74:348-52 pubmed publisher
    ..These results suggest significant risk modifying effects of CTLA-4 -1722C/T, -1661A/G, -318T/C, CT60 A/G and 49A/G SNPs in tobacco-related OSCC in North Indian population. ..
  54. Kim H, Jeong K, Lee S, Moon J, Lee T, Kang S, et al. Polymorphisms of the CTLA4 gene and kidney transplant rejection in Korean patients. Transpl Immunol. 2010;24:40-4 pubmed publisher
    ..013, OR=2.02, 95% CI=1.15-3.52). One CTLA4 gene polymorphism was associated with susceptibility to late acute rejection in kidney transplantation in Korean patients. ..
  55. Ei Wafai R, Chmaisse H, Makki R, Fakhoury H. Association of HLA class II alleles and CTLA-4 polymorphism with type 1 diabetes. Saudi J Kidney Dis Transpl. 2011;22:273-81 pubmed
    ..In addition, several studies have suggested that polymorphisms in the CTLA-4 gene (IDDM12) on chromosome 2q33 form part of the genetic susceptibility for type 1 diabetes...
  56. Gao J, Guo Y, Fan Y, Qiu J, Bao E, Liu Y, et al. Polymorphisms in cytotoxic T lymphocyte associated antigen-4 influence the rate of acute rejection after renal transplantation in 167 Chinese recipients. Transpl Immunol. 2012;26:207-11 pubmed publisher
  57. Alfadhli S. Overexpression and secretion of the soluble CTLA-4 splice variant in various autoimmune diseases and in cases with overlapping autoimmunity. Genet Test Mol Biomarkers. 2013;17:336-41 pubmed publisher
    ..mCTLA-4 and sCTLA-4 mRNA expression were analyzed using quantitative real time-PCR. The enzyme-linked immunosorbent assay (ELISA) was used to screen sCTLA-4 in all subjects' sera...
  58. Liu C, Jiang J, Wang T, Liu X, Gao L, Zhu R, et al. CTLA-4 and CD86 genetic variants and haplotypes in patients with rheumatoid arthritis in southeastern China. Genet Mol Res. 2013;12:1373-82 pubmed publisher
    ..We failed to find any significant association of the 2 CD86 SNPs with RA. These results indicate that the polymorphisms of CTLA-4 (rs5742909) may be important genetic factors for RA risk in the southeastern Han Chinese population. ..
  59. Wang L, Su G, Zhao X, Cai Y, Cai X, Zhang J, et al. Association between the cytotoxic T-lymphocyte antigen 4 +49A/G polymorphism and bladder cancer risk. Tumour Biol. 2014;35:1139-42 pubmed publisher
    ..This is the first study to highlight the significant association between CTLA-4 +49A/G polymorphism and bladder cancer risk. Additional studies are needed to confirm this finding. ..
  60. Salvi S, Fontana V, Boccardo S, Merlo D, Margallo E, Laurent S, et al. Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer. Cancer Immunol Immunother. 2012;61:1463-72 pubmed publisher
    ..We presume that this effect relies on modulation of the interaction of microscopic disease with CTLA-4-ligands expressing cells leading to NSCLC cell death. ..
  61. Taha Khalaf A, Song J, Gao T, Yu X, Lei T. CTLA-4 gene polymorphism and the risk of systemic lupus erythematosus in the Chinese population. J Biomed Biotechnol. 2011;2011:167395 pubmed publisher
    ..4% versus 42.2%). On the contrary, no association was found between SLE and CTLA-4 polymorphism at position -1661. ..
  62. Yang M, Sun T, Zhou Y, Wang L, Liu L, Zhang X, et al. The functional cytotoxic T lymphocyte-associated Protein 4 49G-to-A genetic variant and risk of pancreatic cancer. Cancer. 2012;118:4681-6 pubmed publisher
    ..64 × 10(-12) ). These results suggest that CTLA-4 49G>A polymorphism is involved in susceptibility to developing pancreatic cancer, alone and in a gene-environment interaction manner. ..
  63. Pawlak E, Karabon L, Wlodarska Polinska I, Jedynak A, Jonkisz A, Tomkiewicz A, et al. Influence of CTLA-4/CD28/ICOS gene polymorphisms on the susceptibility to cervical squamous cell carcinoma and stage of differentiation in the Polish population. Hum Immunol. 2010;71:195-200 pubmed publisher
    ..Our results suggest that the CTLA-4 gene is susceptibility gene to CSCC especially to well-differentiated tumor, while association between CD28 gene polymorphism and disease is restricted only to the well-differentiated CSCC. ..
  64. Duan S, Zhang G, Han Q, Li Z, Liu Z, Chen J, et al. CTLA-4 exon 1 +49 polymorphism alone and in a haplotype with -318 promoter polymorphism may confer susceptibility to chronic HBV infection in Chinese Han patients. Mol Biol Rep. 2011;38:5125-32 pubmed publisher
    ..012) in HBeAg positive chronic hepatitis B. It is indicated that CTLA-4 +49A/G polymorphism alone and in a haplotype with -318C allele may confer susceptibility to chronic HBV infection in Chinese Han patients. ..
  65. Laurent S, Carrega P, Saverino D, Piccioli P, Camoriano M, Morabito A, et al. CTLA-4 is expressed by human monocyte-derived dendritic cells and regulates their functions. Hum Immunol. 2010;71:934-41 pubmed publisher
    ..Taken together, our data provide the first evidence that CTLA-4 receptor is expressed by human monocyte-derived mDCs upon their full activation and that it exerts immune modulatory effects. ..
  66. Zhao S, Pan C, Cao H, Han B, Shi J, Liang J, et al. Association of the CTLA4 gene with Graves' disease in the Chinese Han population. PLoS ONE. 2010;5:e9821 pubmed publisher
    ..These data suggest that the susceptibility variants of the CTLA4 gene varied between the different geographic populations with GD...
  67. Thye T, Scarisbrick G, Browne E, Chinbuah M, Gyapong J, Osei I, et al. CTLA4 autoimmunity-associated genotype contributes to severe pulmonary tuberculosis in an African population. PLoS ONE. 2009;4:e6307 pubmed publisher
    ..002, P(cor) = 0.00045, P = 0.0005, respectively). This finding suggests that an increased T-cell activity associated with the CTLA4 +6230G allele contributes to pathology rather than to protection in pulmonary TB. ..
  68. Welsh M, Applebaum K, Spencer S, Perry A, Karagas M, Nelson H. CTLA4 variants, UV-induced tolerance, and risk of non-melanoma skin cancer. Cancer Res. 2009;69:6158-63 pubmed publisher
    ..In conclusion, genetic variation at the CTLA4 locus may be etiologically important in NMSC, the most prevalent malignancy in the United States. ..
  69. Simone R, Brizzolara R, Chiappori A, Milintenda Floriani F, Natale C, Greco L, et al. A functional soluble form of CTLA-4 is present in the serum of celiac patients and correlates with mucosal injury. Int Immunol. 2009;21:1037-45 pubmed publisher
    ..In gluten-exposed patients, serum sCTLA-4 levels might provide insight about mucosal injury. ..
  70. Kozik P, Francis R, Seaman M, Robinson M. A screen for endocytic motifs. Traffic. 2010;11:843-55 pubmed publisher
    ..Thus, the repertoire of endocytic motifs is more extensive than the three well-characterized sorting signals. ..
  71. Zhu J, Li B, Chen G, Feng C, Cen H, Fan Y, et al. CTLA-4 -1722T/C polymorphism and systemic lupus erythematosus susceptibility: a meta-analysis involving ten separate studies. Immunol Invest. 2013;42:91-105 pubmed publisher
    ..09, 95% CI = 1.13-3.85, P = 0.018; T/C VS C/C: OR = 1.53, 95% CI = 0.87-2.69, P = 0.141; T/T VS T/C: OR = 1.42, 95% CI = 0.97-2.09, P = 0.070). In summary, the CTLA-4 -1722T/C polymorphism confers to SLE risk, especially in Asians. ..
  72. Tang M, Zhou Z. Association of the CTLA-4 +49A/G polymorphism with rheumatoid arthritis in Chinese Han population. Mol Biol Rep. 2013;40:2627-31 pubmed publisher
    ..Our results suggested that the CTLA-4 gene might contribute to the pathogenesis of RA, and the +49A/G polymorphism of this gene was a risk factor associated with increased RA susceptibility in Chinese Han population. ..
  73. Oh K, Kang M, Choi W, Kwon J, Kim B, Yu J, et al. Association Between Serum IgE Levels and the CTLA4 +49A/G and FCER1B -654C/T Polymorphisms in Korean Children With Asthma. Allergy Asthma Immunol Res. 2010;2:127-33 pubmed publisher
    ..In addition, Dp/Df-specific IgE levels with a FCER1B -654C/T polymorphism may involve additive effects. ..
  74. Repnik K, Potocnik U. CTLA4 CT60 single-nucleotide polymorphism is associated with Slovenian inflammatory bowel disease patients and regulates expression of CTLA4 isoforms. DNA Cell Biol. 2010;29:603-10 pubmed publisher
    ..034). Our genotype and gene expression data suggest that CTLA4 plays a role in IBD pathogenesis. Polymorphism CTLA4 CT60 contributes to genetic susceptibility to IBD in Slovenian population and regulates expression of CTLA4 isoforms. ..
  75. Simone R, Tenca C, Fais F, Luciani M, De Rossi G, Pesce G, et al. A soluble form of CTLA-4 is present in paediatric patients with acute lymphoblastic leukaemia and correlates with CD1d+ expression. PLoS ONE. 2012;7:e44654 pubmed publisher
    ..This suggests a possible role of this soluble molecule as a marker of progression or severity of the neoplastic disease. ..
  76. Kuo H, Liang C, Yu H, Wang C, Lin I, Liu C, et al. CTLA-4, position 49 A/G polymorphism associated with coronary artery lesions in Kawasaki disease. J Clin Immunol. 2011;31:240-4 pubmed publisher
    ..This study provides the first evidence supporting the association of CTLA-4 (+49) A/G polymorphism with the CAL formation of KD particularly in female patients. ..
  77. Zhang Y, Zhang J, Deng Y, Tian C, Li X, Huang J, et al. Polymorphisms in the cytotoxic T-lymphocyte antigen 4 gene and cancer risk: a meta-analysis. Cancer. 2011;117:4312-24 pubmed publisher
    ..To further evaluate gene-gene and gene-environment interactions between CTLA-4 polymorphisms and the risk of cancer, more studies with larger groups of patients will be required. ..
  78. Wing K, Yamaguchi T, Sakaguchi S. Cell-autonomous and -non-autonomous roles of CTLA-4 in immune regulation. Trends Immunol. 2011;32:428-33 pubmed publisher
    ..Here we discuss how CTLA-4 expression by one T cell can influence the activation of another in a cell non-autonomous fashion and thus control immune responses. ..
  79. Riccio A, Saverino D, Pesce G, Rogkakou A, Severino M, Bonadonna P, et al. Effects of different up-dosing regimens for hymenoptera venom immunotherapy on serum CTLA-4 and IL-10. PLoS ONE. 2012;7:e37980 pubmed publisher
    ..It has been shown that the circulating form of CTLA-4 is elevated in patients with hymenoptera allergy and can be down regulated by immunotherapy...
  80. Yang J, Qin Q, Yan N, Zhu Y, Li C, Yang X, et al. CD40 C/T(-1) and CTLA-4 A/G(49) SNPs are associated with autoimmune thyroid diseases in the Chinese population. Endocrine. 2012;41:111-5 pubmed publisher
    ..262). These results indicate that both CTLA-4 A/G(49) and CD40 C/T(-1) SNPs are associated with genetic susceptibility of GD, and CTLA-4 A/G(49) is also associated with HT...
  81. Feng D, Yang X, Li S, Liu T, Wu Z, Song Y, et al. Cytotoxic T-lymphocyte antigen-4 genetic variants and risk of Ewing's sarcoma. Genet Test Mol Biomarkers. 2013;17:458-63 pubmed publisher
    ..004). These results indicated that the CTLA-4 polymorphism could be a risk factor for ES and suggested a potential role of CTLA-4 in the metastasis of this malignancy. ..