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Single nucleotide polymorphisms of IL12B are associated with Takayasu arteritis in Chinese Han population

  • Genes and Disease
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Abstract

Takayasu arteritis (TA) is a rare autoimmune disease of unknown etiology. Genome-wide association studies (GWAS) have demonstrated association between genetic variants of IL12B and IL6 and TA. Since TA has been reported with ethnic heterogeneity, we sought to investigate whether the single-nucleotide-polymorphisms (SNPs) reported in these studies are associated with TA in the Chinese Han population. A multi-center study involving 412 patients with TA and 597 healthy controls was conducted. Sequenom MassArray iPLEX platform was used to determine the frequencies of SNPs in the IL12B and IL6 region. We demonstrated a allele association between the four SNPs of IL12B and TA (rs6871626: OR 1.52, 95% CI 1.26–1.83; rs4921492: OR 1.46, 95% CI 1.21–1.75; rs60689680: OR 1.41, 95% CI 1.17–1.69; rs4921493: OR 1.45, 95% CI 1.21–1.75, all P c  < 10− 3 ). A meta-analysis consist of four populations showed rs6871626 was a susceptible locus of TA. Its OR was 1.51, and 95% CI was 1.31–1.74. The four SNPs were in strong linkage disequilibrium and two haplotypes were significantly different between patients and controls. Conditional analysis shows that these SNPs were not independent factors contributing to TA. Nevertheless, neither genotype nor allele frequencies of rs2069837 in IL6 showed significant between-group differences. Thus SNP of IL12B may be considered a high-risk factor for TA in Chinese Han population and provide further clues for research into the pathogenesis of TA.

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Acknowledgements

We thank Lv Guanting in Beijing DNALead Co. LTD and all our colleagues who contributed to the TA study.

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    Authors and Affiliations

    1. Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China

      Xiaoting Wen, Si Chen, Ping Li, Jing Li, Ziyan Wu, Yuan Li, Liubing Li, Xinping Tian, Fengchun Zhang & Yongzhe Li

    2. Department of Clinical Laboratory, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China

      Si Chen & Hui Yuan

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    1. Xiaoting Wen
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    2. Si Chen
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    Correspondence to Yongzhe Li.

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    Conflict of interest

    All authors declare that there are no conflicts of interest.

    Ethnical approval

    The study was approved by the Ethics Committee at the Peking Union Medical College Hospital; all participants gave informed consent.

    Funding

    This work was supported by the Research Special Fund for Public Welfare Industry of Health (201202004); the National Natural Science Foundation of China Grants (81172857, 81373188); the Chinese National High Technology Research and Development Program, Ministry of Science and Technology Grants (2011AA02A113); the National Science Technology Pillar Program in the 12th 5-year Plan (2014BAI07B00), and the Capital Health Research and Development of Special (2014-1-4011).

    Additional information

    X. Wen, S. Chen and P. Li contributed equally to this work.

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    Wen, X., Chen, S., Li, P. et al. Single nucleotide polymorphisms of IL12B are associated with Takayasu arteritis in Chinese Han population. Rheumatol Int 37, 547–555 (2017). https://doi.org/10.1007/s00296-016-3648-3

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    • DOI: https://doi.org/10.1007/s00296-016-3648-3

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