Erscheint 6 Ausgaben pro Jahr
ISSN Druckformat: 1045-4403
ISSN Online: 2162-6502
Indexed in
Meta-Analysis of CTLA-4 +49 Gene Polymorphism and Susceptibility to Graves' Disease
ABSTRAKT
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays an important role in the initiation and development of Graves' disease (GD), especially CTLA-4 +49A/G polymorphism and genetic susceptibility to GD. However, the current conclusions are consistent. Therefore, this study adopted meta-analysis method to assess the exact correlation between this polymorphism and GD risk.
Methods: Literature searches were performed in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Wanfang, and other databases for data on the correlation between polymorphisms of CTLA-4 +49A/G and GD risk. The end date for publications was May 2020. Stata 15.0 software was used for data analysis.
Results: A total of 33 papers were included, covering 8,555 cases and 9,533 controls. The results showed that the CTLA-4 +49 allele G compared to allele A, odds ratio (OR) = 1.62, 95% CI [1.56, 2.09]. In the dominant, recessive, homozygous, and heterozygous genetic models, comparing the GD group and the control group, the combined OR was 1.81, 95% CI [1.56, 2.09]; 1.91, 95% CI [1.66, 2.21]; 2.75, 95% CI, [2.21, 3.41]; and 1.49, 95% CI [1.29, 1.71], respectively. When it was analyzed by dividing genetic models into subgroups according to ethnicity and published year, the data the of genetic model in each subgroup were also statistically significant.
Conclusion: The CTLA-4 +49A/G polymorphism was strongly associated with genetic susceptibility to GD. Allele G, genotypes GG, GG + GA, and GA are correlated with an increase in the risk of GD.
-
Antonelli A, Fallahi P, Elia G, Ragusa F, Paparo SR, Ruf- filli I, Patrizio A, Gonnella D, Giusti C, Virili C, Centanni M, Shoenfeld Y, Ferrari SM. Graves' disease: Clinical manifestations, immune pathogenesis (cytokines and chemokines) and therapy. Best Pract Res Clin Endocrinol Metab. 2020;34(1):101388.
-
Burch HB, Cooper DS. Management of Graves disease: A review. JAMA. 2015;314(23):2544-54.
-
Wemeau JL, Klein M, Sadoul JL, Briet C, Velayoudom-Cephise FL. Graves' disease: Introduction, epidemiology, endogenous and environmental pathogenic factors. Ann Endocrinol (Paris). 2018;79(6):599-607.
-
Dong YH, Fu DG. Autoimmune thyroid disease: Mechanism, genetics and current knowledge. Eur Rev Med Pharmacol Sci. 2014;18(23):3611-8.
-
Brix TH, Hegedus L. Twin studies as a model for exploring the aetiology of autoimmune thyroid disease. Clin Endocrinol (Oxf). 2012;76(4):457-64.
-
Han XR, Wen X, Wang S, Fan SH, Zhuang J, Wang YJ, Zhang ZF, Li MQ, Hu B, Shan Q, Sun CH, Bao YX, Wu DM, Lu J, Zheng YL. Correlations of CTLA-4 exon-1 49 A/G and promoter region 318C/T polymorphisms with the therapeutic efficacy of 131I radionuclide in Graves' disease in Chinese Han population. J Cell Biochem. 2018;119(8):6383-90.
-
Lombardi A, Menconi F, Greenberg D, Concepcion E, Leo M, Rocchi R, Marino M, Keddache M, Tomer Y. Dissecting the genetic susceptibility to Graves' disease in a cohort of patients of Italian origin. Front Endocrinol (Lausanne). 2016;7:21.
-
Walunas TL, Lenschow DJ, Bakker CY, Linsley PS, Freeman GJ, Green JM, Thompson CB, Bluestone JA. CTLA-4 can function as a negative regulator of T cell activation. Immunity. 1994;1(5):405-13.
-
Mossallam GI, Samra MA. CTLA-4 polymorphism and clinical outcome post allogeneic hematopoietic stem cell transplantation. Hum Immunol. 2013;74(12):1643-8.
-
Eliana F, Suwondo P, Asmarinah A, Harahap A, Djauzi S, Prihartono J, TGD Pemayun. The role of cytotoxic T-ly mphocy te-associated protein 4 (CTLA-4) gene, thyroid stimulating hormone receptor (TSHR) gene and regulatory T-cells as risk factors for relapse in patients with Graves disease. Acta Med Indones. 2017;49(3):195-204.
-
Donner H, Rau H, Walfish PG, Braun J, Siegmund T, Finke R, Herwig J, Usadel KH, Badenhoop K. CTLA4 alanine-17 confers genetic susceptibility to Graves' disease and to type 1 diabetes mellitus. J Clin Endocrinol Metab. 1997;82(1):143-6.
-
Kouki T, Gardine CA, Yanagawa T, DeGroot LJ. Relation of three poly morphisms of the CTLA-4 gene in patients with Graves' disease. J Endocrinol Invest. 2002;25(3):208-13.
-
Frydecka I, Daroszewski J, Suwalska K, Zoledziowska M, Tutak A, Slowik M, Potoczek S, Dobosz T. CTLA-4 (CD152) gene poly morphism at position 49 in exon 1 in Graves' disease in a Polish population of the Lower Silesian region. Arch Immunol Ther Exp (Warsz). 2004;52(5):369-74.
-
Kacem HH, Bellassoued M, Bougacha-Elleuch N, Abid M, Ay adi H. CTLA-4 gene poly morphisms in Tunisian patients with Graves' disease. Clin Immunol. 2001;101(3):361-5.
-
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603-5.
-
Park YJ, Chung HK, Park DJ, Kim WB, Kim SW, Koh JJ, Cho BY. Polymorphism in the promoter and exon 1 of the cytotoxic T lymphocyte antigen-4 gene associated with autoimmune thy roid disease in Koreans. Thy roid. 2000;10(6):453-9.
-
Bednarczuk T, Hiromatsu Y, Fukutani T, Jazdzewski K, Miskiewicz P, Osikowska M, Nauman J. Association of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene polymorphism and non-genetic factors with Graves' ophthalmopathy in European and Japanese populations. Eur J Endocrinol. 2003;148(1):13-8.
-
Vaidya B, Oakes EJC, Imrie H, Dickinson AJ, Perros P, Kendall-Taylor P, Pearce SHS. CTLA4 gene and Graves' disease: Association of Graves' disease with the CTLA4 exon 1 and intron 1 polymorphisms, but not with the promoter polymorphism. Clin Endocrinol (Oxf). 2003;58(6):732-5.
-
Petrone A, Giorgi G, Galgani A, Alemanno I, Corsello SM, Signore A, Di Mario U, Nistico L, Cascino I, Buzzetti R. CT60 Single nucleotide polymorphisms of the cytotoxic T-lymphocyte-associated antigen-4 gene region is associated with Graves' disease in an Italian population. Thyroid. 2005;15(3):232-8.
-
Han S, Zhang S, Zhang W, Li R, Li Y, Wang Z, Xie Y, Mao Y. CTLA4 Polymorphisms and ophthalmopathy in Graves' disease patients: Association study and meta-analysis. Hum Immunol. 2006;67(8):618-26.
-
Kimura H, Kato Y, Shimizu S, Takano K, Sato K. Association of polymorphism at position 49 in exon 1 of the cytotoxic T-lymphocyte-associated factor 4 gene with Graves' disease refractory to medical treatment, but not with amiodarone-associated thyroid dysfunction. Thyroid. 2009;19(9):975-81.
-
Esteghamati A, Khalilzadeh O, Mobarra Z, Anvari M, Tahvildari M, Amiri HM, Rashidi A, Solgi G, Parivar K, Nikbin B, Amirzargar A. Association of CTLA-4 gene polymorphism with Graves' disease and ophthalmopathy in Iranian patients. Eur J Intern Med. 2009;20(4):424-8.
-
Jurecka-Lubieniecka B, Ploski R, Kula D, Krol A, Bednarczuk T, Kolosza Z, Tukiendorf A, Szpak-Ulczok S, Stanjek-Cichoracka A, Polanska J, Jarzab B. Association between age at diagnosis of Graves' disease and variants in genes involved in immune response. PLoS One. 2013;8(3):e59349.
-
Sahin M, Erdogan MF, Erdogan G. Cytotoxic T lymphocyte-associated molecule-4 polymorphisms in Turkish Graves' disease patients and association with probability of remission after antithyroid therapy. Eur J Intern Med. 2005;16(5):352-5.
-
Shehjar F, Dil-Afroze, Misgar RA, Malik SA, Laway BA. A significant association of the CTLA4 gene variants with the risk of autoimmune Graves' disease in ethnic Kashmiri population. Cell Immunol. 2020;347:103995.
-
Fathima N, Narne P, Ishaq M. Association and gene-gene interaction analyses for polymorphic variants in CTLA-4 and FOXP3 genes: Role in susceptibility to autoimmune thyroid disease. Endocrine. 2019;64(3):591-604.
-
Ramgopal S, Rathika C, Padma MR, Murali V, Arun K, Kamaludeen MN, Balakrishnan K. Interaction of HLA-DRB1 alleles and CTLA4 (+49 AG) gene polymorphism in autoimmune thyroid disease. Gene. 2018;642:430-8.
-
Chen X, Hu Z, Liu M, Li H, Liang C, Li W, Bao L, Chen MY, Wu G. Correlation between CTLA-4 and CD40 gene polymorphisms and their interaction in graves' disease in a Chinese Han population. BMC Med Genet. 2018;19(1):171.
-
Fouad NA, Saeed AM, Mahedy AW. Association of CTLA-4 +49 A/G and CT60 gene polymorphism with Graves' disease. Egypt J Immunol. 2017;24(2):63-70.
-
Tu Y, Fan G, Yu D, Zeng T, Xiao F, Chen L, Wen K. Association between rs3087243 and rs231775 polymorphism within the cytotoxic T-lymphocyte antigen 4 gene and Graves' disease: A case/control study combined with meta-analyses. Oncotarget. 2017;8(66): 110614-24.
-
Ting WH, Chien MN, Lo FS, Wang C, Huang C, Lin C, Lin WS, Chang TY, Yang HW, Chen WF, Lien YP, Cheng BW, Lin CH, Chen CC, Wu YL, Hung CM, Li HJ, Chan CI, Lee YJ. Association of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene polymorphisms with autoimmune thyroid disease in children and adults: Case-control study. PLoS One. 2016;11(4):e154394.
-
Wang L, Wang F, Ma RX, Yu HW. Study of the A/G49 polymorphism of CTLA-4 gene exon 1 in autoimmune thyroid diseases. Immunol J. 2001;17(2):116-8.
-
Wang QH, Ren YZ. Association of polymorphism of CTLA-4 gene exon 1 with Graves' disease in Chinese population. Chin J Endocrinol Metab. 2003;19(41):297-9.
-
Du YT, Zhang Q, Li M, Zhang P, Qiu MC. Study on the relativity of leukopenia and cytotoxic T lymphocyte associated antigen-4 gene polymorphism in Graves' disease. Tianjin Med J. 2005;33(10):624-6.
-
Yao B, Hao LM, Yan JH, Weng JP, Li YB. Association between the CTLA-4 gene polymorphism and Graves' disease in the Southern Chinese Han population. Chin J Endocrinol Metab. 2006;22(4):363-4.
-
Guo ZQ, Chen XM, Wu G, Su M, Jie YL, Wu MF, Wu XM. Association in the polymorphism of cytotoxic T lymphocyte antigen-4 gene and the hereditary susceptibility to Graves' disease and Graves' ophthalmopathy of Han population in western region of Guangdong province. Curr Immunol. 2010;30(2):151-4.
-
Qu RY, Li SX, Zheng J, Liu W, Liu BL, Song ZY. Association between CTLA-4 gene polymorphisms and the susceptibility to Graves' disease. Chin J Endocrinol Metab. 2014;30(1):35-7.
-
Weng YC, Wu MJ, Lin WS. CT60 single nucleotide poly-morphism of the CTLA-4 gene is associated with susceptibility to Graves' disease in the Taiwanese population. Ann Clin Lab Sci. 2005;35(3):259-64.
-
Yung E, Cheng PS, Fok TF, Wong GWK. CTLA-4 gene A-G polymorphism and childhood Graves' disease. Clin Endocrinol. 2002;56(5):649-53.
-
Cho HJ, Chung JH, Kim IS, Kim HJ, Cho SH, Ki CS, Kim JW. Lack of a genetic association between the CTLA-4 gene and Graves' disease in Koreans. Thyroid. 2006;16(3):237-41.
-
Wang PW, Chen IY, Liu RT, Hsieh CJ, Hsi E, Juo SHH. Cytotoxic T lymphocyte-associated molecule-4 gene polymorphism and hyperthyroid Graves' disease relapse after antithyroid drug withdrawal: A follow-up study. J Clin Endocrinol Metab. 2007;92(7):2513-8.
-
Yang J, Qin Q, Yan N, Zhu YF, Li C, Yang XJ, Wang X, Pandey M, Hou P, Zhang JA. CD40 C/Tj and CTLA-4 A/G49 SNPs are associated with autoimmune thyroid diseases in the Chinese population. Endocrine. 2012; 41(1):111-5.
-
Kouki T, Sawai Y, Gardine CA, Fisfalen ME, Alegre ML, Degroot LJ. CTLA-4 gene polymorphism at position 49 in exon 1 reduces the inhibitory function of CTLA-4 and contributes to the pathogenesis of Graves' disease. J Immunol. 2000;165(11):6606-11.
-
Heward JM, Allahabadia A, Armitage M, Hattersley A, Dodson PM, Macleod K, Carr-Smith J, Daykin J, Daly A, Sheppard MC, Holder RL, Barnett AH, Franklyn JA, Gough SC. The development of Graves' disease and the CTLA-4 gene on chromosome 2q33. J Clin Endocrinol Metab. 1999;84(7):2398-401.
-
Aversa T, Corica D, Zirilli G, Pajno GB, Salzano G, De Luca F, Wasniewska M. Phenotypic expression of auto- immunity in children with autoimmune thyroid disorders. Front Endocrinol (Lausanne). 2019;10:476.
-
Shukla SK, Singh G, Ahmad S, Pant P. Infections, genetic and environmental factors in pathogenesis of autoimmune thyroid diseases. Microb Pathogen. 2018;116:279-88.
-
Kolar P, Knieke K, Hegel JKE, Quandt D, Burmester GR, Hoff H, Brunner-Weinzier MC. CTLA-4 (CD152) controls homeostasis and suppressive capacity of regulatory T cells in mice. Arthritis Rheum. 2009;60(1):123-32.
-
Garcia-Mayor RV, Alvarez-Vazquez P, Fluiters E, Valverde D, Andrade A. Long-term remission following antithyroid drug withdrawal in patients with Graves' hyperthyroidism: Parameters with prognostic value. Endocrine. 2019;63(2):316-22.
-
Bossowski A, Stasiak-Barmuta A, Urban M. Relationship between CTLA-4 and CD28 molecule expression on T lymphocytes and stimulating and blocking autoantibodies to the TSH-receptor in children with Graves' disease. Horm Res. 2005;64(4):189-97.
-
Kavvoura FK, Akamizu T, Awata T, Ban Y, Chistiakov DA, Frydecka I, Ghaderi A, Gough SC, Hiromatsu Y, Plo- ski R, Wang PW, Ban Y, Bednarczuk T, Chistiakova EI, Chojm M, Heward JM, Hiratani H, Jou SHH, Karabon L, Katayama S, Kurihara S, Liu RT, Miyake I, Omrani GHR, Pawlak E, Taniyama M, Tozaki T, Ioannidis JPA. Cytotoxic T-lymphocyte associated antigen 4 gene polymorphisms and autoimmune thyroid disease: A meta-analysis. J Clin Endocrinol Metab. 2007;92(8):3162-70.