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Association between IKZF1 related gene polymorphism, DNA methylation and rheumatoid arthritis in Han Chinese: A case-control study.
  • +11
  • dong li,
  • Xinxia Sui,
  • Qingzhi Hou,
  • Xia Feng,
  • Yanru Chen,
  • Xueyu Chen,
  • Yuejin Li,
  • Xiaohui Wang,
  • Xiaojun Wang,
  • Tan Tan,
  • WenRan Zhang,
  • Zhaoyang Tang,
  • Jian Lv,
  • Long Ji
dong li
Shandong First Medical University & Shandong Academy of Medical Sciences
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Xinxia Sui
Shandong First Medical University & Shandong Academy of Medical Sciences
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Qingzhi Hou
Shandong First Medical University & Shandong Academy of Medical Sciences
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Xia Feng
Shandong First Medical University & Shandong Academy of Medical Sciences
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Yanru Chen
Shandong First Medical University & Shandong Academy of Medical Sciences
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Xueyu Chen
Shandong First Medical University & Shandong Academy of Medical Sciences
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Yuejin Li
Shandong First Medical University & Shandong Academy of Medical Sciences
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Xiaohui Wang
Shandong First Medical University & Shandong Academy of Medical Sciences
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Xiaojun Wang
Shandong First Medical University & Shandong Academy of Medical Sciences
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Tan Tan
Shandong First Medical University & Shandong Academy of Medical Sciences
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WenRan Zhang
Shandong First Medical University & Shandong Academy of Medical Sciences
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Zhaoyang Tang
Shandong First Medical University & Shandong Academy of Medical Sciences
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Jian Lv
Shandong First Medical University & Shandong Academy of Medical Sciences
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Long Ji
Shandong First Medical University & Shandong Academy of Medical Sciences
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Abstract

Background: Rheumatoid arthritis (RA) is a systematic autoimmune disease with evidence of genetic predisposition. The IKZF1 (IKAROS family zinc finger 1 (Ikaros)) gene is located at chromosome 7, encodes a transcription factor related tochromatin remodeling, regulates lymphocyte differentiation, and is associated with some autoimmune diseases. However, there were few studies reported the association between IKZF1 and the risk of RA in China. For this, we determined to investigate the possibility of association between the IKZF1 locus and RA. Methods: we selected one single nucleotide polymorphisms (SNP) in the IKZF1 locus, rs1456893, based on a detailed analysis of genome-wide association study (GWAS) data and performed genotyping in 410 RA patients and 421 healthy controls in Han Chinese. We studied the systematic genome-wide interrogation of DNA methylation between RA group and control group and we also studied the association between CpGs and RA. Results: The results showed that the rs1456893 locus was correlated with RA in different models(P<0.05). Through comparison with methylation levels determined in their equivalent healthy counterparts we have identified and validated a restricted set of CpGs that show distinct methylation differences between patients with RA and control group. The Multiple logistic regression results showed CpG_3 (OR=3.17,95%CI=1.05-9.60,P=0.041) and CpG_13.14(OR=4.96,95%CI=1.77-13.86,P=0.002)were associated with RA. Conclusion: IKZF1 can be used as a marker for the diagnosis of RA. Higher CpG_3 and CpG_13.14 methylation levels would increase the risk of RA.