您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2017, Vol. 55 ›› Issue (5): 95-102.doi: 10.6040/j.issn.1671-7554.0.2016.1196

• 临床医学 • 上一篇    下一篇

STAT4 rs7574865位点单核苷酸多态性与系统性红斑狼疮易感性Meta分析

杜金阁1,陈慧2,杨孝荣1,吕明1,2   

  1. 1.山东大学公共卫生学院流行病学系, 山东 济南 250012;2.山东大学齐鲁医院科研处临床流行病学研究室, 山东 济南 250012
  • 收稿日期:2016-09-23 出版日期:2017-05-10 发布日期:2017-05-10
  • 通讯作者: 吕明. E-mail:lvming@sdu.edu.cn E-mail:lvming@sdu.edu.cn

Meta-analysis of the association between the STAT4 rs7574865 polymorphism and systemic lupus erythematosus

DU Jinge1, CHEN Hui2, YANG Xiaorong1, LÜ Ming1,2   

  1. 1. Department of Epidemiology, School of Public Health, Shandong University, Jinan 250012, Shandong, China;
    2. Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Received:2016-09-23 Online:2017-05-10 Published:2017-05-10

摘要: 目的 通过Meta分析探讨信号转导和转录激活因子4(STAT4)基因rs7574865位点单核苷酸多态性(SNP)与系统性红斑狼疮(SLE)易感性之间的关系。 方法 两名研究者分别检索PubMed、Web of science、Scopus、中国知网和万方数据库,筛选出相关文献。用合并OR值和95% CI评价STAT4 rs7574865位点SNP与SLE易感性之间的关系。 结果 共纳入27篇研究,包含21 902例SLE患者和37 780例对照。Meta分析结果如下:等位基因模型(T vs G, OR=1.56, 95% CI:1.49~1.63),纯合子模型(TT vs GG, OR=2.32, 95% CI:2.08~2.58),杂合子模型(TG vs GG, OR=1.52, 95% CI:1.41~1.64),显性遗传模型(TT/TG vs GG, OR=1.67, 95% CI:1.55~1.79),隐性遗传模型(TT vs TG/GG, OR=1.83, 95% CI:1.65~2.02)。按研究对象所在的地区进行亚组分析后显示,所有亚组中,rs7574865 SNP均与SLE易感性有关。 结论 STAT4 rs7574865位点SNP与SLE的易感性有关,T等位基因的存在增加SLE的患病风险。

关键词: 系统性红斑狼疮, STAT4, 基因多态性, 单核苷酸多态性, Meta分析

Abstract: Objective To assess the association between STAT4 rs7574865 single nucleotide polymorphism and systemic lupus erythematosus by a Meta-analysis. Methods Two authors searched PubMed, Web of science, Scopus, China National Knowledge Infrastructure(CNKI)and Wanfang databases to identify relevant studies, independently. Odds ratio(OR)with 95% confidence interval(CI)were calculated to assess the strength of the association between rs7574865 polymorphism and SLE risk. Results A total of 27 studies were eventually included in this meta-analysis, which contained 21 902 SLE cases and 37 780 controls. Pooled analyses showed significant association between STAT4 rs7574865 polymorphism and SLE risk using allelic model(T vs G, OR=1.56, 95% CI: 1.49-1.63), homozygote model(TT vs GG, OR=2.32, 95% CI: 2.08-2.58), heterozygote model(TG vs GG, OR=1.52, 95% CI: 1.41-1.64), dominant model(TT/TG vs GG, OR=1.67, 95% CI: 1.55-1.79)and recessive model(TT vs TG/GG, OR=1.83, 95% CI: 1.65-2.02). In the subgroup analysis by region, evidences also showed significant association between rs7574865 polymorphism and SLE risk in all regions. Conclusion STAT4 rs7574865 G>T polymorphism correlate with an increased risk of SLE and the T allele may be a risk factor.

Key words: STAT4, Gene polymorphism, Single nucleotide polymorphism, Meta-analysis, Systemic lupus erythematosus

中图分类号: 

  • R181.3
[1] 冯金保. 中国汉族人群信号转导和转录激活因子-4基因单核苷酸多态性与系统性红斑狼疮的家系关联研究[D]. 合肥:安徽医科大学, 2010. FENG Jinbao. Family-based association study beween human STAT4 genes single nucleotide polymorphism with SLE in Chinese Han population[D]. Hefei: Anhui Medical University, 2010.
[2] Thakral A, Klein-Gitelman MS. An update on treatment and management of pediatric systemic lupus erythematosus[J]. Rheumatol Ther, 2016, 3(2): 209-219.
[3] Barton A, Thomson W, Ke X, et al. Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility[J]. Hum Mol Genet, 2008, 17(15): 2274-2279.
[4] Orozco G, Alizadeh BZ, Delgado-Vega AM, et al. Association of STAT4 with rheumatoid arthritis: a replication study in three European populations[J]. Arthritis Rheum, 2008, 58(7): 1974-1980.
[5] Zervou MI, Sidiropoulos P, Petraki E, et al. Association of a TRAF1 and a STAT4 gene polymorphism with increased risk for rheumatoid arthritis in a genetically homogeneous population[J]. Hum Immunol, 2008, 69(9): 567-571.
[6] Graham RR, Hom G, Ortmann W, et al. Review of recent genome-wide association scans in lupus[J]. J Intern Med, 2009, 265(6): 680-688.
[7] Mathur AN, Chang HC, Zisoulis DG, et al. Stat3 and Stat4 direct development of IL-17-secreting Th cells[J]. J Immunol, 2007, 178(8): 4901-4907.
[8] Wang Y, Miller S, Roulston D, et al. Genome-wide single-nucleotide polymorphism array analysis improves prognostication of acute lymphoblastic leukemia/lymphoma[J]. J Mol Diagn, 2016, 18(4): 595-603.
[9] Yousry SM, Shahin RM, EI Refai RM. Contribution of protein Z gene single-nucleotide polymorphism to systemic lupus erythematosus in Egyptian patients[J]. Blood Coagul Fibrinolysis, 2016, 27(6): 691-695.
[10] Watford WT, Hissong BD, Bream JH, et al. Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4[J]. Immunol Rev, 2004, 202(1): 139-156.
[11] Leoncini E, Carioli G, La Vecchia C, et al. Risk factors for neuroendocrine neoplasms: a systematic review and meta-analysis[J]. Ann Oncol, 2016, 27(1): 68-81.
[12] Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses[J]. BMJ, 2003, 327(7414): 557-560.
[13] Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease[J]. J Natl Cancer Inst, 1959, 22(4): 719-748.
[14] Dersimonian R, Kacker R. Random-effects model for meta-analysis of clinical trials: an update[J]. Contemp Clin Trials, 2007, 28(2): 105-114.
[15] Harbord RM, Egger M, Sterne JA. A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints[J]. Stat Med, 2006, 25(20): 3443-3457.
[16] Peters JL, Sutton AJ, Jones DR, et al. Performance of the trim and fill method in the presence of publication bias and between-study heterogeneity[J]. Stat Med, 2007, 26(25): 4544-4562.
[17] Raafat II, Azab NA, Khorshied MM, et al. Signal transducer and activator of transcription4(STAT4)G/T gene polymorphism in Egyptian systemic lupus erythematosus female patients[J]. The Egyptian Rheumatologist, 2015, 37(2): 75-80.
[18] Dang J, Shan S, Li J, et al. Gene-gene interactions of IRF5, STAT4, IKZF1 and ETS1 in systemic lupus erythematosus[J]. Tissue Antigens, 2014, 83(6): 401-408.
[19] Ciccacci C, Perricone C, Ceccarelli F, et al. A multilocus genetic study in a cohort of Italian SLE patients confirms the association with STAT4 gene and describes a new association with HCP5 gene[J]. PLoS One, 2014, 9(11): e111991. doi: 10.1371/journal.pone.0111991.
[20] Chai HC, Chua KH, Lim SK, et al. Insight into gene polymorphisms involved in toll-like receptor/interferon signalling pathways for systemic lupus erythematosus in South East Asia[J]. J Immunol Res, 2014, 529167. doi: 10.1155/2014/529167.
[21] Mirkazemi S, Akbarian M, Jamshidi AR, et al. Association of STAT4 rs7574865 with susceptibility to systemic lupus erythematosus in Iranian population[J]. Inflammation, 2013, 36(6): 1548-1552.
[22] Kadota K, Mori M, Yanagimachi M, et al. Analysis of gender differences in genetic risk: association of TNFAIP3 polymorphism with male childhood-onset systemic lupus erythematosus in the Japanese population[J]. PLoS One, 2013, 8(8): e72551. doi: 10.1371/journal.pone.0072551.
[23] Luan H, Li P, Cao C, et al. A single-nucleotide polymorphism of the STAT4 gene is associated with systemic lupus erythematosus(SLE)in female Chinese population[J]. Rheumatol Int, 2012, 32(5): 1251-1255.
[24] Sanchez E, Comeau ME, Freedman BI, et al. Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study[J]. Arthritis Rheum, 2011, 63(11): 3493-3501.
[25] Koga M, Kawasaki A, Ito I, et al. Cumulative association of eight susceptibility genes with systemic lupus erythematosus in a Japanese female population[J]. J Hum Genet, 2011, 56(7): 503-507.
[26] Chung SA, Taylor KE, Graham RR, et al. Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production[J]. PLoS Genet, 2011, 7(3): e1001323. doi: 10.1371/journal.pgen.1001323.
[27] Yang W, Shen N, Ye DQ, et al. Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus[J]. PLoS Genet, 2010, 6(2):e1000841. doi: 10.1371/journal.pgen.1000841.
[28] Su Y, Zhao Y, Liu X, et al. Variation in STAT4 is associated with systemic lupus erythematosus in Chinese Northern Han population[J]. Chin Med J(Engl), 2010,123(22):3173-3177.
[29] Sanchez E, Webb RD, Rasmussen A, et al. Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus[J]. Arthritis Rheum, 2010, 62(12): 3722-3729.
[30] Yang W, Ng P, Zhao M, et al. Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese[J]. Genes Immun, 2009, 10(3): 219-226.
[31] Suarez-Gestal M, Calaza M, Endreffy E, et al. Replication of recently identified systemic lupus erythematosus genetic associations: a case-control study[J]. Arthritis Res Ther, 2009, 11(3): R69. doi: 10.1186/ar2698.
[32] Kiyohara C, Washio M, Horiuchi T, et al. Cigarette smoking, STAT4 and TNFRSF1B polymorphisms, and systemic lupus erythematosus in a Japanese population[J]. J Rheumatol, 2009, 36(10): 2195-2203.
[33] Han JW, Zheng HF, Cui Y, et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus[J]. Nat Genet, 2009, 41(11): 1234-1237.
[34] Abelson AK, Delgado-Vega AM, Kozyrev SV, et al. STAT4 associates with systemic lupus erythematosus through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk[J]. Ann Rheum Dis, 2009, 68(11): 1746-1753.
[35] Palomino-Morales RJ, Rojas-Villarraga A, Gonzalez CI, et al. STAT4 but not TRAF1/C5 variants influence the risk of developing rheumatoid arthritis and systemic lupus erythematosus in Colombians[J]. Genes Immun, 2008, 9(4): 379-382.
[36] Kobayashi S, Ikari K, Kaneko H, et al. Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population[J]. Arthritis Rheum, 2008, 58(7): 1940-1946.
[37] Taylor KE, Remmers EF, Lee AT, et al. Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus[J]. PLoS Genet, 2008, 4(5):e1000084. doi: 10.1371/journal.pgen.1000084.
[38] Kawasaki A, Ito I, Hikami K, et al. Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population: a case-control association study of the STAT1-STAT4 region[J]. Arthritis Res Ther, 2008, 10(5): R113. doi: 10.1186/ar2516.
[39] Harley JB, Alarcon-Riquelme ME, Criswell LA, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci[J]. Nat Genet, 2008, 40(2): 204-210.
[40] Remmers EF, Plenge RM, Lee AT, et al. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus[J]. N Engl J Med, 2007, 357(10): 977-986.
[41] 柏素云, 张立民, 王翠香, 等. STAT4基因单核苷酸多态性与系统性红斑狼疮关系的研究[J]. 免疫学杂志, 2010, 26(2): 183-185. BAI Suyun, ZHANG Limin, WANG Cuixiang, et al. The association between STAT4 rs7574865 single nucleotide polymorphism and SLE[J]. Immunological Journal, 2010, 26(2):183-185.
[42] 缪倩, 唐元家, 钱晓霞, 等. 中国汉族人群系统性红斑狼疮患者信号传导和转录激活子4基因多态性研究[J]. 中华风湿病学杂志, 2009, 13(8): 516-520. MIAO Qian, TANG Yuanjia, QIAN Xiaoxia, et al. STAT4 gene polymorphism in Chinese Han systemic lupus erythematosus[J]. Chin J Rheumatol, 2009, 13(8): 516-520.
[43] Beltran Ramirez O, Mendoza Rincon JF, Barbosa Cobos RE, et al. STAT4 confers risk for rheumatoid arthritis and systemic lupus erythematosus in Mexican patients[J]. Immunol Lett, 2016, 175: 40-43. doi: 10.1016/j.imlet.2016.05.003.
[44] 杨小蕾. STAT4基因多态性与云南汉族人群SLE发病的相关性研究[D]. 昆明:昆明医学院, 2011. YANG Xiaolei. Associated study between polymorphisms of STAT4 and systemic lupus erythematosus in the Han population of Yunan province[D]. Kunming: Kunming Medical University, 2011.
[45] 王丽. mtDNA单倍型M/N及核SNP STAT4rs3821236与湖南汉族女性SLE的相关性研究[D]. 长沙:中南大学, 2014. WANG Li. Association analysis of mtDNA haplogroup M/N and STAT4 rs3821236 to systemic lupus erythematosus risk in Han females from Hunan province[D]. Changsha: Central South University, 2014.
[46] Ji JD, Lee WJ, Kong KA, et al. Association of STAT4 polymorphism with rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis[J]. Mol Biol Rep, 2010, 37(1): 141-147.
[47] Liang YL, Wu H, Shen X, et al. Association of STAT4 rs7574865 polymorphism with autoimmune diseases: a meta-analysis[J]. Mol Biol Rep, 2012, 39(9): 8873-8882.
[1] 葛丽娟 金瑞峰 王纪文 许新升 李癊. 多药耐药基因1 C1236T多态性与癫痫患者对药物反应性的相关性[J]. 山东大学学报(医学版), 2209, 47(6): 99-102.
[2] 温学龙,刘安慧,陈经纬,吴梦婷,杨岷. 急性非ST抬高型心肌梗死行冠状动脉旁路移植手术时机Meta分析[J]. 山东大学学报 (医学版), 2025, 63(5): 60-70.
[3] 侯晓慧,Arezou Bikdeli,马超,李大庆. 250例NSTE-ACS患者ACE、KLK1及PTGIS基因型联合相关性分析[J]. 山东大学学报 (医学版), 2025, 63(2): 10-20.
[4] 杜凯豪,侯立朝,东小鸽,薛伟伟,何洁洁,罗兰明慧,蒋威,汪占金,王展. 东亚人肠道菌群与胰腺癌关系:基于孟德尔随机化方法的遗传学证据[J]. 山东大学学报 (医学版), 2025, 63(12): 44-52.
[5] 杨春桃,左玉. MMP1、MMP9基因与慢性牙周炎的因果关系:基于两样本孟德尔随机化研究[J]. 山东大学学报 (医学版), 2025, 63(11): 87-97.
[6] 刘向荣,张新胜,杨荩冉,杨雪艳,刘钊,刘英华. ω-6/ω-3多不饱和脂肪酸比值对不同肿瘤发病风险的系统综述和Meta分析[J]. 山东大学学报 (医学版), 2024, 62(8): 34-48.
[7] 康随芳,王迎雪,张琪晨,王志仑,尹哲,肖娟,陈国玲. 系统性红斑狼疮患者睑板腺形态和功能的异常及其对泪膜的影响[J]. 山东大学学报 (医学版), 2024, 62(6): 65-70.
[8] 徐洪波,胡仁琴,田茂强,冉潇,陈艳. PIK3CD基因杂合突变所致新表型——系统性红斑狼疮[J]. 山东大学学报 (医学版), 2023, 61(1): 113-117.
[9] 秦静,杨飞,陈谦,夏涵岱,刘延国,王秀问. 晚期驱动基因阴性、PD-L1表达阴性非鳞非小细胞肺癌一线治疗方案的网状Meta分析[J]. 山东大学学报 (医学版), 2022, 60(7): 74-82.
[10] 成晅,杨帆,潘正论. 系统性红斑狼疮、抗磷脂抗体综合征伴颅内静脉窦血栓形成1例并文献复习[J]. 山东大学学报 (医学版), 2022, 60(6): 70-74.
[11] 孔林笑语,孙书珍,余丽春,贾梦文. 188例儿童系统性红斑狼疮5年生存率及预后分析[J]. 山东大学学报 (医学版), 2022, 60(12): 69-76.
[12] 高青,鲁婷,单珊,陶靖,金华. 364例孕早中期自然流产组织单核苷酸多态性微阵列分析[J]. 山东大学学报 (医学版), 2022, 60(10): 68-73.
[13] 国云飞,舒强. 免疫抑制剂在风湿病相关复发性流产中的应用[J]. 山东大学学报 (医学版), 2021, 59(8): 38-43.
[14] 张琳,王燕,马旭,范雪松,袁慧. 不稳定心绞痛患者亚甲基四氢叶酸还原酶基因多态性与血清同型半胱氨酸的相关性[J]. 山东大学学报 (医学版), 2021, 59(6): 71-75.
[15] 孟朝暾,李钦, 孙卉,邬信芳,孙文凯,高伟. 白细胞介素18单核苷酸多态性与73例喉鳞状细胞癌易感性的关联性[J]. 山东大学学报 (医学版), 2020, 1(9): 58-63.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!