Correlation between Chinese Population Cytotoxic T Lymphocytes Associated Antigen-4 Gene Exon-1 & Promoter Polymorphisms and Graves’ Disease: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

CHEN Xiaowen ,  LILing

The First Affiliated Hospital of Anhui College of Traditional Chinese Medicine, Anhui 230061, China;

Corresponding author：

LILing, Email: 640347226@qq.com

Keywords：

CTLA-4; Polymorphism; Graves’ disease; Chinese population; Systematic review; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.20120204

Video：

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Objective 　To systematically evaluate correlation between exon-1 (locus 49, A/G) and promoter (locus -318, C/T) polymorphisms of Chinese population cytotoxic T lymphocytes associated antigen-4 (CTLA-4) gene and Graves’ Disease (GD).
Methods 　Relevant studies were electronically searched in CNKI, VIP, CBM, PubMed, EMbase and The Cochrane Library from 1980.1 to 2011.12. According to the inclusion and exclusion criteria, we selected and screened all case-control studies on the correlation between CTLA-4 exon -1 (locus 49, A/G) and promoter (locus -318, C/T) polymorphisms of Chinese population and GD. Then we extracted the data and assessed the methodological quality of the included studies. Meta-analysis was performed using RevMan 5.0 and STATA 12.0 software.
Results 　(1) Ten studies on exon-1 were included. Results of meta-analyses showed that Chinese population with genotype G/G had a higher GD risk than those with genotype A/A (OR=3.38, 95%CI 2.07 to 5.51) and A/G (OR=1.72, 95%CI 1.31 to 2.25). Also, the allele G showed significant association with increased GD risk compared to the allele A (OR=1.87, 95%CI 1.44 to 2.41). (2) Five studies on promoter-318 were included. Results of meta-analyses showed that Chinese population with genotype T/T presented no increased relative risk compared to those with genotype C/C (OR=0.75, 95%CI 0.26 to 2.12) or C/T (OR=0.92, 95%CI 0.31 to 2.73). Meanwhile, the allele T showed no increased relative risk compared to the allele C (OR=0.83, 95%CI 0.61 to 1.12).
Conclusion 　The allele G at the locus 49 of exon -1 of Chinese population is significantly associated with increased GD risks, yet the correlation between promoter –318 C/T polymorphism and GD hasn’t been demonstrated. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to test the above conclusion.

Citation： CHEN Xiaowen,LILing. Correlation between Chinese Population Cytotoxic T Lymphocytes Associated Antigen-4 Gene Exon-1 & Promoter Polymorphisms and Graves’ Disease: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2012, 12(11): 1302-1308. doi: 10.7507/1672-2531.20120204 Copy

1.	Zeitlin AA, Heward JM, Newby PR, et al. Analysis of HLA classⅡ genes in Hashimoto’s thyroiditis reveals differences compared to Graves’ disease. Genes Immun, 2008, 9(4): 358-363.
2.	姚斌, 郝李敏, 严晋华, 等. 细胞毒性T淋巴细胞相关抗原4基因型与中国南方人群Graves’病的关系. 中山大学学报, 2005, 26(6): 654-658.
3.	Little J, Higgins JP, Ioannidis JP, et al. Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement. Eur J Epidemiol, 2009, 24(1): 37-55.
4.	王静, 莫传伟, 陈群, 等. 应用Stata软件的Meta分析完成医学科研定量评价. 中华中医药学刊, 2008, 26(5): 947-949.
5.	刘晓民, 于晶琳, 苏颖, 等. CTLA-4基因外显子1位点49多态性与Graves’病的关联研究. 哈尔滨医科大学学报, 2002, 6: 447.
6.	姜博仁. 山东地区汉族人CTLA-4基因外显子1多态性与Graves病及辩证分型的相关性研究. 山东: 山东中医药大学, 2005.
7.	杜亦陶, 张勤, 李梅, 等. Graves病白细胞减少与CTLA-4基因多态性的相关性. 天津医药, 2005, 33(10): 624-626.
8.	姚斌, 郝李敏, 严晋华, 等. CTLA-4基因多态性与中国南方汉族人Graves病的相关性. 中华内分泌代谢杂志, 2006, 22(4): 363-364.
9.	余绮玲, 陈定宇, 肖正华, 等. 广东人汉族群CTLA-4基因外显子1多态性与Graves病的相关性. 解剖学研究, 2006, 28(4): 278-280.
10.	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 Univ Sci B, 2006, 7(11): 887-891.
11.	于志云, 张进安, 买尔哈巴, 等. PTPN22基因多态性与自身免疫甲状腺病的相关性. 细胞与分子免疫学杂志, 2008, 24(8): 804-807.
12.	康毓芝, 杨宝珍, 王立斌, 等. 宁夏地区Graves’病与CTLA-4基因多态性相关性研究. 检验医学, 2010, 25(4): 292-295.
13.	郭中秋, 陈晓铭, 吴平, 等. CTLA-4基因多态性与粤西汉族人Graves病发病的相关性研究. 广东医学院学报, 2010, 28(1): 1-3.
14.	侯新, 毛金媛, 李玉妹, 等. CTLA4基因与中国汉族Graves病的相关性研究. 中华医学会第十次全国内分泌学学术会议论文汇编, 2011: 158.
15.	张卉, 闫胜利, 王娈, 等. CTLA-4基因启动子318位点C/T多态性与抗甲状腺药物导致白细胞减少的相关性. 免疫学杂志, 2010, 26(12): 1070-1073.
16.	康德英, 王家良. Meta分析结果评价. 王家良, 主编. 循证医学. 第2版. 北京: 人民卫生出版社, 2011: 90-91.
17.	王丹, 牟振云, 翟俊霞, 等. Stata软件在Meta-分析发表性偏倚识别中的探讨. 现代预防医学, 2008, 35(15): 2819-2822.
18.	段丽君, 张墨玲, 陈昆明. T细胞调节基因CTLA-4与自身免疫性甲状腺疾病遗传易感性. 中国地方病学杂志, 2004, 23(6): 627-629.
19.	Anjos S, Nguyen A, Ounissi-Benkalha H, et al. A common autoimmunity predisposing signal peptide variant of the cytotoxic T-lymphocyte antigen 4 results in inefficient glycosylation of the susceptibility allele. J Biol Chem, 2002, 277(48): 46478-46486.
20.	王淑琼, 高继东, 张惠莉. CTLA-4基因多态性与弥漫性毒性甲状腺肿的相关性. 青海医学院学报, 2010, 31(4): 225-227.
21.	Zaletel K, Krhin B, Gaberscek S, et al. Thyroid autoantibody production is influenced by exon 1 and promoter CTLA-4 polymorphisms in patients with Hashimoto’s thyroiditis. Int J Immunogenet, 2006, 33(2): 87-91.

1. Zeitlin AA, Heward JM, Newby PR, et al. Analysis of HLA classⅡ genes in Hashimoto’s thyroiditis reveals differences compared to Graves’ disease. Genes Immun, 2008, 9(4): 358-363.
2. 姚斌, 郝李敏, 严晋华, 等. 细胞毒性T淋巴细胞相关抗原4基因型与中国南方人群Graves’病的关系. 中山大学学报, 2005, 26(6): 654-658.
3. Little J, Higgins JP, Ioannidis JP, et al. Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement. Eur J Epidemiol, 2009, 24(1): 37-55.
4. 王静, 莫传伟, 陈群, 等. 应用Stata软件的Meta分析完成医学科研定量评价. 中华中医药学刊, 2008, 26(5): 947-949.
5. 刘晓民, 于晶琳, 苏颖, 等. CTLA-4基因外显子1位点49多态性与Graves’病的关联研究. 哈尔滨医科大学学报, 2002, 6: 447.
6. 姜博仁. 山东地区汉族人CTLA-4基因外显子1多态性与Graves病及辩证分型的相关性研究. 山东: 山东中医药大学, 2005.
7. 杜亦陶, 张勤, 李梅, 等. Graves病白细胞减少与CTLA-4基因多态性的相关性. 天津医药, 2005, 33(10): 624-626.
8. 姚斌, 郝李敏, 严晋华, 等. CTLA-4基因多态性与中国南方汉族人Graves病的相关性. 中华内分泌代谢杂志, 2006, 22(4): 363-364.
9. 余绮玲, 陈定宇, 肖正华, 等. 广东人汉族群CTLA-4基因外显子1多态性与Graves病的相关性. 解剖学研究, 2006, 28(4): 278-280.
10. 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 Univ Sci B, 2006, 7(11): 887-891.
11. 于志云, 张进安, 买尔哈巴, 等. PTPN22基因多态性与自身免疫甲状腺病的相关性. 细胞与分子免疫学杂志, 2008, 24(8): 804-807.
12. 康毓芝, 杨宝珍, 王立斌, 等. 宁夏地区Graves’病与CTLA-4基因多态性相关性研究. 检验医学, 2010, 25(4): 292-295.
13. 郭中秋, 陈晓铭, 吴平, 等. CTLA-4基因多态性与粤西汉族人Graves病发病的相关性研究. 广东医学院学报, 2010, 28(1): 1-3.
14. 侯新, 毛金媛, 李玉妹, 等. CTLA4基因与中国汉族Graves病的相关性研究. 中华医学会第十次全国内分泌学学术会议论文汇编, 2011: 158.
15. 张卉, 闫胜利, 王娈, 等. CTLA-4基因启动子318位点C/T多态性与抗甲状腺药物导致白细胞减少的相关性. 免疫学杂志, 2010, 26(12): 1070-1073.
16. 康德英, 王家良. Meta分析结果评价. 王家良, 主编. 循证医学. 第2版. 北京: 人民卫生出版社, 2011: 90-91.
17. 王丹, 牟振云, 翟俊霞, 等. Stata软件在Meta-分析发表性偏倚识别中的探讨. 现代预防医学, 2008, 35(15): 2819-2822.
18. 段丽君, 张墨玲, 陈昆明. T细胞调节基因CTLA-4与自身免疫性甲状腺疾病遗传易感性. 中国地方病学杂志, 2004, 23(6): 627-629.
19. Anjos S, Nguyen A, Ounissi-Benkalha H, et al. A common autoimmunity predisposing signal peptide variant of the cytotoxic T-lymphocyte antigen 4 results in inefficient glycosylation of the susceptibility allele. J Biol Chem, 2002, 277(48): 46478-46486.
20. 王淑琼, 高继东, 张惠莉. CTLA-4基因多态性与弥漫性毒性甲状腺肿的相关性. 青海医学院学报, 2010, 31(4): 225-227.
21. Zaletel K, Krhin B, Gaberscek S, et al. Thyroid autoantibody production is influenced by exon 1 and promoter CTLA-4 polymorphisms in patients with Hashimoto’s thyroiditis. Int J Immunogenet, 2006, 33(2): 87-91.

Chinese Journal of Evidence-Based Medicine

Correlation between Chinese Population Cytotoxic T Lymphocytes Associated Antigen-4 Gene Exon-1 & Promoter Polymorphisms and Graves’ Disease: A Meta-Analysis

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