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Open Access 01-12-2013 | Research article

The associations between the polymorphisms in the CTLA-4gene and the risk of Graves’ disease in the Chinese population

Authors: Liang Du, Jiqiao Yang, Jichong Huang, Yaxian Ma, Haichuan Wang, Tianyuan Xiong, Zhangpeng Xiang, Yonggang Zhang, Jin Huang

Published in: BMC Medical Genetics | Issue 1/2013

Abstract

Background

The associations between the polymorphisms in Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) gene and Graves’ disease (GD) have been extensively investigated in Chinese population. However, the results were inconsistent. The objective of this study is to investigate the associations between the polymorphisms in CTLA-4 gene and the risk of GD by meta-analysis.

Methods

We searched Pubmed database, Medline (Ovid) database, CNKI database and Wanfang database, covering all studies until August 11, 2012. Statistical analysis was performed by using the Revman4.2 software and the Stata10.0 software.

Results

A total of 28 case–control studies concerning the most widely studied three polymorphisms [+49A/G(rs231775), -318C/T(rs5742909) and CT60(rs3087243)] for Chinese population in 21 publications were included. The results suggested that the G allele carriers (GG+GA) might have an increased risk of GD when compared with the AA homozygote carriers for the +49A/G polymorphism (GG+GA vs. AA: OR = 2.57, 95%CI = 1.87-3.52). However, as to the -318C/T polymorphism and CT60 polymorphism, the results indicated that the variant allele carriers might have decreased risks of GD when compared with the homozygote carriers (−318C/T: TT+TC vs. CC: OR = 0.78, 95%CI = 0.62-0.97; CT60: AA+AG vs. GG: OR = 0.64, 95%CI = 0.52-0.78).

Conclusions

The current meta-analysis indicated that the polymorphisms in the CLTA-4 gene might be risk factors for GD in the Chinese population. In future, more large-scale case–control studies are needed to validate these results.

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Wen-Ling L, Rong-Hsing C, Hui-Ju L, Yu-Huei L, Wen-Chi C, Yuhsin T, Lei W, Fuu-Jen T: Toll-like receptor gene polymorphisms are associated with susceptibility to graves’ ophthalmopathy in Taiwan males. BMC Med Genet. 2010, 11: 154-10.1186/1471-2350-11-154.CrossRef

Han SZ, Zhang SH, Li R, Zhang WY, Li Y: The common − 318C/T polymorphism in the promoter region of CTLA4 gene is associated with reduced risk of ophthalmopathy in Chinese Graves’ patients. Int J Immunogenet. 2006, 33 (4): 281-287. 10.1111/j.1744-313X.2006.00614.x.CrossRefPubMed

Chu X, Dong Y, Shen M, Sun L, Dong C, Wang Y, Wang B, Zhang K, Hua Q, Xu S: Polymorphisms in the ADRB2 gene and Graves disease: a case–control study and a meta-analysis of available evidence. BMC Med Genet. 2009, 10 (1): 26-CrossRefPubMedPubMedCentral

Dechairo BM, Zabaneh D, Collins J, Brand O, Dawson GJ, Green AP, Mackay I, Franklyn JA, Connell JM, Wass JAH: Association of the TSHR gene with Graves’ disease: the first disease specific locus. Eur J Hum Genet. 2005, 13 (11): 1223-1230. 10.1038/sj.ejhg.5201485.CrossRefPubMed

Zhao SX, Pan CM, Cao HM, Han B, Shi JY, Liang J, Gao GQ, Peng YD, Su Q, Chen JL: Association of the CTLA4 gene with Graves’ disease in the Chinese Han population. PLoS One. 2010, 5 (3): e9821-10.1371/journal.pone.0009821.CrossRefPubMedPubMedCentral

Hiromatsu Y, Fukutani T, Ichimura M, Mukai T, Kaku H, Nakayama H, Miyake I, Shoji S, Koda Y, Bednarczuk T: Interleukin-13 gene polymorphisms confer the susceptibility of Japanese populations to Graves’ disease. J Clin Endocrinol Metab. 2005, 90 (1): 296-301.CrossRefPubMed

Mayans S, Lackovic K, Nyholm C, Lindgren P, Ruikka K, Eliasson M, Cilio C, Holmberg D: CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden. BMC Med Genet. 2007, 8 (1): 3-CrossRefPubMedPubMedCentral

Kotsa K, Watson PF, Weetman AP: A CTLA‐4 gene polymorphism is associated with both Graves’ disease and autoimmune hypothyroidism. Clin Endocrinol (Oxf). 1997, 46 (5): 551-554. 10.1046/j.1365-2265.1997.1710996.x.CrossRef

Zhang YG, Li XB, Zhang J, Huang J, He C, Tian C, Deng Y, Wan H, Shrestha D, Yang YY: The I/D polymorphism of angiotensin‐converting enzyme gene and asthma risk: a meta-analysis. Allergy. 2011, 66 (2): 197-205. 10.1111/j.1398-9995.2010.02438.x.CrossRefPubMed

10.

Chong KK, Chiang SW, Wong GW, Tam PO, Ng TK, Hu YJ, Yam GH, Lam DS, Pang CP: Association of CTLA-4 and IL-13 gene polymorphisms with Graves’ disease and ophthalmopathy in Chinese children. Invest Ophthalmol Vis Sci. 2008, 49 (6): 2409-2415. 10.1167/iovs.07-1433.CrossRefPubMed

11.

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. Tian Jin Yi Yao (Chinese). 2005, 33 (10): 624-626.

12.

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. Xian Dai Mian Yi Xue (Chinese). 2010, 30 (2): 151-154.

13.

Jiang BR: Association of polymorphsim of CTLA-4 gene exon 1 with Graves’ disease and TCM syndrome differentiation in Chinese Shandong province population. 2005, http://d.wanfangdata.com.cn/Thesis_Y724586.aspx.

14.

Kang YZ, Yang BZ, Wang LB, Wu RF, Shi ZY: Research on the correlation of gene polymorphism of cytotoxic T lymphocyte · associated antigen 4 and Graves’disease in Ningxia. Jian Yan Yi Xue (Chinese). 2010, 25 (4): 292-295.

15.

Shen FX, Wang DW, Quan JX, Jiang L, Zhang HL, Feng WH: Relationship between of thyroid associated ophthalmopathy and T-lymphocyte-associated antigen-4 gene A/G polymorphism at position 49 in exon 1. Wen Zhou Yi Xue Yuan Xue Bao (Chinese). 2005, 35 (5): 356-358.

16.

Tsai ST, Huang CY, Lo FS, Chang YT, Tanizawa T, Chen CK, Wang ZC, Liu HF, Chu CC, Lin M: Association of CT60 polymorphism of the CTLA4 gene with Graves’ disease in Taiwanese children. J Pediatr Endocrinol Metab. 2008, 21 (7): 665-672.CrossRefPubMed

17.

Wang L, Yu HW, Yan SL, Zhao SH, Wang YG, Wang P: The association of cytotoxic T lymphocyte-associated antigen 4 gene polymorphism with type 1 diabetes mellitus and autoimmune thyroid disease in Chinese Han population. Zhong Hua Nei Fen Mi Dai Xie Za Zhi (Chinese). 2001, 17 (4): 228-231.

18.

Wang PW, Chen IY, Liu RT, Hsieh CJ, Hsi E, Juo SH: 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): 2513-2518. 10.1210/jc.2006-2761.CrossRefPubMed

19.

Wang QH, Ren YZ: Association of polymorphism of CTLA-4 gene exon 1 with Graves’ disease in Chinese population. Zhong Hua Nei Fen Mi Dai Xie Za Zhi (Chinese). 2003, 19 (4): 297-299.

20.

Wang SQ, Gao JD, Zhang HL: Association of CTLA-4 gene exon 1 polymorphism with Graves’ disease in Han population. Qing Hai Yi Xue Yuan Xue Bao (Chinese). 2010, 31 (4): 225-227.

21.

Weng YC, Wu MJ, Lin WS: CT60 single nucleotide polymorphism of the CTLA-4 gene is associated with susceptibility to Graves’ disease in the Taiwanese population. Ann Clin Lab Sci. 2005, 35 (3): 259-PubMed

22.

Yang J, Qin Q, Yan N, Zhu YF, Li C, Yang XJ, Wang X, Pandey M, Hou P, Zhang JA: CD40 C/T(−1) and CTLA-4 A/G(49) SNPs are associated with autoimmune thyroid diseases in the Chinese population. Endocrine. 2012, 41 (1): 111-115. 10.1007/s12020-011-9510-1.CrossRefPubMed

23.

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. Zhong Hua Nei Fen Mi Dai Xie Za Zhi (Chinese). 2006, 22 (4): 363-364.

24.

Yu QL, Chen DY, Xiao ZH, Wang Y: Association of polymorphism of CTLA-4 gene exon 1 with Graves’ disease in Cantonese Han population. Jie Pou Xue Yan Jiu (Chinese). 2006, 28 (4): 278-280.

25.

Yu ZY, Zhang JA, Maier HB, Wang Y, Xiao WX, Quan Y, Dong BN: Assoc ia tion of polymorphism of prote in tyrosine phosphatase nonreceptor222 gene with AITD. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi (Chinese). 2008, 24 (8): 804-807.

26.

Zhang H, Yan SL, Wang L, Qi YQ: Relatio nship between CTLA-4 gene promoter region −318 site C/T polymorphism and the leukopenia caused by antithyroid drug. Mian Yi Xue Za Zhi (Chinese). 2010, 26 (12): 1070-1073.

27.

Zhang JL, Yan SL: CTLA-4 gene 49A/G polymorphism is associated with relapse of Graves’ disease. Zhong Hua Nei Fen Mi Dai Xie Za Zhi (Chinese). 2008, 24 (2): 192-193.

28.

Zhang Q, Yang Y, Lv X: Association of Graves’ disease and Graves’ ophthalmopathy with the polymorphisms in promoter and exon 1 of cytotoxic T lymphocyte associated antigen-4 gene. J Zhejiang University-Sci B. 2006, 7 (11): 887-891. 10.1631/jzus.2006.B0887.CrossRef

29.

Marissa PM, Elizabeth RL, Inka R, Heinrich K, Stefanie H, Holger W, Christian S, Maria S, Klaus B: The rs1990760 polymorphism within the IFIH1 locus is not associated with Graves’ disease. Hashimoto’s thyroiditis and Addison’s disease. BMC Med Genet. 2009, 10: 126-10.1186/1471-2350-10-126.CrossRef

30.

Braun J, Donner H, Siegmund T, Walfish PG, Usadel KH, Badenhoop K: CTLA‐4 promoter variants in patients with Graves’ disease and Hashimoto’s thyroiditis. Tissue Antigens. 1998, 51 (5): 563-566. 10.1111/j.1399-0039.1998.tb02993.x.CrossRefPubMed

31.

Ueda H, Howson JMM, Esposito L, Heward J, Snook GC, Rainbow DB, Hunter KMD, Smith AN, Di Genova G, Herr MH: Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature. 2003, 423 (6939): 506-511. 10.1038/nature01621.CrossRefPubMed

32.

Jacobson EM, Tomer Y: The CD40, CTLA-4, thyroglobulin, TSH receptor, and PTPN22 gene quintet and its contribution to thyroid autoimmunity: Back to the future. J Autoimmun. 2007, 28 (2): 85-98. 10.1016/j.jaut.2007.02.006.CrossRefPubMedPubMedCentral

33.

Vaidya B, Oakes E, Imrie H, Dickinson AJ, Perros P, Kendall Taylor P, Pearce S: 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): 732-735. 10.1046/j.1365-2265.2003.01778.x.CrossRef

34.

Esteghamati A, Khalilzadeh O, Mobarra Z, Anvari M, Tahvildari M, Amiri HM, Rashidi A, Solgi G, Parivar K, Nikbin B: Association of CTLA-4 gene polymorphism with Graves’ disease and ophthalmopathy in Iranian patients. Eur J Intern Med. 2009, 20 (4): 424-428. 10.1016/j.ejim.2008.12.005.CrossRefPubMed

35.

Chang MC, Chang YT, Tien YW, Liang PC, Jan IS, Wei SC, Wong JM: T-cell regulatory gene CTLA-4 polymorphism/haplotype association with autoimmune pancreatitis. Clin Chem. 2007, 53 (9): 1700-1705. 10.1373/clinchem.2007.085951.CrossRefPubMed

36.

Chu X, Dong C, Lei R, Sun L, Wang Z, Dong Y, Shen M, Wang Y, Wang B, Zhang K: Polymorphisms in the interleukin 3 gene show strong association with susceptibility to Graves’ disease in Chinese population. Genes Immun. 2009, 10 (3): 260-266. 10.1038/gene.2009.3.CrossRefPubMed

37.

Guo T, Yang S, Liu N, Wang S, Cui B, Ning G: Association study of interleukin‐12A gene polymorphisms with Graves’ disease in two Chinese populations. Clin Endocrinol (Oxf). 2011, 74 (1): 125-129. 10.1111/j.1365-2265.2010.03905.x.CrossRef

38.

Liu N, Lu H, Tao F, Guo T, Liu C, Cui B, Ning G: An association of interleukin-10 gene polymorphisms with Graves’ disease in two Chinese populations. Endocrine. 2011, 40 (1): 90-94. 10.1007/s12020-011-9444-7.CrossRefPubMed

39.

Pan TR, Xing SM: Association of TNF-α gene polymorphisms with Graves disease susceptibility and early course thyroid stimulating hormone receptor antibody level in Chinese Han population in Anhui region. Zhonghua Yi Xue Yi Chuan Xue Za Zhi (Chinese). 2012, 29 (3): 347-351.

40.

Matsuda A, Kishi T, Jacob A, Aziz M, Wang P: Association between insertion/deletion polymorphism in angiotensin-converting enzyme gene and acute lung injury/acute respiratory distress syndrome: a meta-analysis. BMC Med Genet. 2012, 13 (1): 76-CrossRefPubMedPubMedCentral

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/14/46/prepub

Title: The associations between the polymorphisms in the CTLA-4gene and the risk of Graves’ disease in the Chinese population
Authors: Liang Du
Jiqiao Yang
Jichong Huang
Yaxian Ma
Haichuan Wang
Tianyuan Xiong
Zhangpeng Xiang
Yonggang Zhang
Jin Huang
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2013
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-14-46

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The associations between the polymorphisms in the CTLA-4gene and the risk of Graves’ disease in the Chinese population

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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