Hu Li-Ya, Cheng Zhi, Zhang Bo, Yin Qiong, Zhu Xiao-Wei, Zhao Pian-Pian, Han Ming-Yu, Wang Xiao-Bo, Zheng Hou-Feng
Institute of Aging Research and the Affiliated Hospital, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
Suzhou Science and Technology Town Hospital, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China.
Arch Dermatol Res. 2017 Aug;309(6):461-477. doi: 10.1007/s00403-017-1745-0. Epub 2017 May 20.
Previous studies have explored the relationship of PTPN22 and TLR9 polymorphisms with systemic lupus erythematosus (SLE). In consideration of the population stratification, conflicting results and updating data, we conducted a comprehensive meta-analysis, which consists of a total of 17 research articles (9120 cases and 11,724 controls) for PTPN22 and 20 articles (including up to 2808 cases and 3386 controls) for TLR9. Significant association was verified between PTPN22 rs2476601 and SLE in the overall population (OR = 1.511 per T allele, 95% CI 1.338-1.706, P = 2.931 × 10) and under dominant model of T allele (TT+CT vs. CC: OR = 1.531, 95% CI 1.346-1.742, P = 9.17 × 10). Analysis after stratification by ethnicity indicated that PTPN22 rs2476601 was related to SLE in Americans (OR = 2.566, 95% CI 1.796-3.665, P = 2.219 × 10), Europeans (OR = 1.399, 95% CI 1.261-1.552, P = 2.153 × 10), and Africans (OR = 4.14, 95% CI 1.753-9.775, P = 1.0 × 10). We did not observe any association between TLR9 polymorphisms (rs187084, rs352140, rs5743836 and rs352139) and SLE under any model, after excluding the data that were inconsistent with Hardy-Weinberg equilibrium (HWE). In summary, PTPN22 rs2476601 was significantly interrelated with SLE and contributed to susceptibility and development of SLE in Americans, Europeans and Africans in this analysis, while their relationship needs to be validated in Africans by future research.
以往的研究探讨了蛋白酪氨酸磷酸酶非受体型22(PTPN22)和Toll样受体9(TLR9)基因多态性与系统性红斑狼疮(SLE)的关系。考虑到人群分层、相互矛盾的结果以及数据更新,我们进行了一项全面的荟萃分析,其中包括总共17篇关于PTPN22的研究文章(9120例病例和11724例对照)以及20篇关于TLR9的文章(包括多达2808例病例和3386例对照)。在总体人群中,PTPN22 rs2476601与SLE之间存在显著关联(每个T等位基因的比值比[OR]=1.511,95%置信区间[CI]为1.338 - 1.706,P = 2.931×10),在T等位基因的显性模型下(TT + CT对CC:OR = 1.531,95%CI为1.346 - 1.742,P = 9.17×10)。按种族分层后的分析表明,PTPN22 rs2476601与美国人群中的SLE相关(OR = 2.566,95%CI为1.796 - 3.665,P = 2.219×10)、欧洲人群中的SLE相关(OR = 1.399,95%CI为1.261 - 1.552,P = 2.153×10)以及非洲人群中的SLE相关(OR = 4.14,95%CI为1.753 - 9.775,P = 1.0×10)。在排除不符合哈迪 - 温伯格平衡(HWE)的数据后,我们未观察到TLR9基因多态性(rs187084、rs352140、rs5743836和rs352139)与SLE在任何模型下存在关联。总之,在本分析中,PTPN22 rs2476601与SLE显著相关,并导致美国、欧洲和非洲人群中SLE的易感性和发病,而它们在非洲人群中的关系有待未来研究验证。