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Associations between PTPN22 and TLR9 polymorphisms and systemic lupus erythematosus: a comprehensive meta-analysis

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Abstract

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 × 10−11) and under dominant model of T allele (TT+CT vs. CC: OR = 1.531, 95% CI 1.346–1.742, P = 9.17 × 10−11). 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 × 10−7), Europeans (OR = 1.399, 95% CI 1.261–1.552, P = 2.153 × 10−10), and Africans (OR = 4.14, 95% CI 1.753–9.775, P = 1.0 × 10−3). 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.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (81501145), the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars of China (LR17H070001), the State Key Development Program for Basic Research of China (973 Program, 2014CB541701), the HZNUARI-Pilot Research Grant. The funding agencies had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank the peer reviewers for their thorough and helpful review of this manuscript.

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  1. Li-Ya Hu, Zhi Cheng and Bo Zhang contributed equally to this work.

Authors and Affiliations

  1. Institute of Aging Research and the Affiliated Hospital, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China

    Li-Ya Hu, Qiong Yin, Xiao-Wei Zhu, Pian-Pian Zhao, Xiao-Bo Wang & Hou-Feng Zheng

  2. Suzhou Science and Technology Town Hospital, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China

    Zhi Cheng

  3. The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

    Bo Zhang

  4. School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland

    Ming-Yu Han

  5. Institute for Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China

    Hou-Feng Zheng

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  1. Li-Ya Hu
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The authors have no competing interests that might be perceived to influence the results and/or discussion reported in this paper. This study re-analyzed the previous published data; therefore, this study did not involve original human participants.

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Hu, LY., Cheng, Z., Zhang, B. et al. Associations between PTPN22 and TLR9 polymorphisms and systemic lupus erythematosus: a comprehensive meta-analysis. Arch Dermatol Res 309, 461–477 (2017). https://doi.org/10.1007/s00403-017-1745-0

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