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Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (6): 1020-1025. doi: 10.19723/j.issn.1671-167X.2021.06.002

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Methylation status and expression of TWEAK gene promoter region in peripheral blood of patients with rheumatoid arthritis

LOU Xue,LIAO Li,LI Xing-jun,WANG Nan,LIU Shuang,CUI Ruo-mei,XU Jian()   

  1. Department of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
  • Received:2021-08-16 Online:2021-12-18 Published:2021-12-13
  • Contact: Jian XU E-mail:casxujian@163.com
  • Supported by:
    National Natural Science Foundation of China(81760296);National Natural Science Foundation of China(81501406);National Natural Science Foundation of China(81460256);Yunnan Provincial Health Science and Technology Plan(2017NS051);Yunnan Provincial Health Science and Technology Plan(2018NS0133);Yunnan Provincial Health Science and Technology Plan(2018NS0134);Yunnan Provincial Fund for High Level Reserve Talents in Health Science(H-2017068);Hundred-Talent Program of Kunming Medical University(60117190457);Youth Talent of Ten Thousand Scientists Program of Yunnan Province(YNWR-QNBJ-2018-152);Yunnan Province High-level Health Technical Talents (Leading Talents)(L-2019004);Yunnan Province Special Project for Famous Medical Talents of the “Ten Thousand Talents Program”(YNWR-MY-2018-040);Yunnan Province Clinical Center for Skin Immune Diseases(ZX2019-03-02);Yunnan Province Clinical Research Center for Skin Immune Diseases(2019ZF012)

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Abstract:

Objective: To explore the relationship between tumor necrosis factor like weak inducer of apoptosis (TWEAK) gene and the pathogenesis of rheumatoid arthritis (RA) by detecting the DNA methylation level, mRNA expression level and serum protein concentration of TWEAK gene in peripheral blood. Methods: The MassARRAY method was used to detect the DNA methylation level of the TWEAK gene in the peripheral blood of 112 RA patients and 86 matched healthy volunteers. The real-time quantitative polymerase chain reaction method was used to detect the mRNA expression level of the TWEAK gene in the peripheral blood of the subjects. The enzyme-linked immunosorbent assay method was used to detect the serum TWEAK protein concentration of the subjects. The TWEAK gene DNA methylation level, mRNA expression level and serum protein concentration between the RA group and the healthy control group were compared, and the relationship between it and the degree of disease activity analyzed. Results: The overall DNA methylation level of TWEAK gene and the DNA methylation levels of CpG_11, CpG_17.18.19.20, CpG_40.41.42 site in the RA group were higher than those in the healthy control group (P=0.002, P=0.01, P=0.006, P=0.002, respectively). The DNA methylation level of CpG_55.56 site in the high disease activity group was higher than that in the medium and low disease activity group (P=0.041). The expression level of TWEAK gene mRNA in the peripheral blood of the RA group was lower than that of the healthy control group (P=0.023). The expression level of TWEAK gene mRNA in the high disease activity group was lower than that in the medium and low disease activity group (P=0.035). The serum TWEAK protein concentration of the RA group was not significantly different from that of the healthy control group (P=0.508), but it was positively correlated with the mRNA expression level (r=0.482, P<0.001). Conclusion: The TWEAK gene is closely related to the onset and progression of RA, and its hypermethylation state may be one of the epigenetic mechanisms regulating its low mRNA expression, and it can be used as one of the important indicators for clinical monitoring and evaluation of RA.

Key words: Tumor necrosis factor-like weak inducer of apoptosis, DNA methylation, mRNA, Rheumatoid arthritis

CLC Number: 

  • R593.22

Figure 1

Comparison of DNA methylation levels at various points in the RA group and the healthy control group RA, rheumatoid arthritis."

Table 1

Comparison of methylation levels between high, medium and low disease activity ($\overline{x}$±s)"

Items High disease
activity group (n=24)		 Medium and low
disease activity group (n=16)		 t value P value
Overall methylation level/% 0.078±0.008 0.077±0.009 -0.579 0.566
CpG_55.56/% 0.241±0.048 0.216±0.028 -2.112 0.041

Figure 2

Correlation between serum TWEAK protein concentration and mRNA expression level"

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