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AB0179 Hypermethylation of HDAC6 Promoter in Systemic Lupus Erythematosus
  1. J.-H. Yen
  1. Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, Province of China

Abstract

Background Genes and environmental factors are involved in the pathogenesis of systemic lupus erythematosus (SLE). DNA methylation and histone modification affect the binding of transcription factors, and alter the expression of eukaryotic genes. HDAC6 is involved in cell migration, immune synapse formation, interfering HIV infection, and degradation of misfolded protein. Methylation of HDAC6 promoter region may affect the protein expression of HDAC6, and then influence the immunological function of HDAC6 and acetylation status of HDAC6-targeted gene.

Objectives To investigate the role of methylation in HDAC6 promoter and HDAC6 mRNA expression in the pathogenesis of SLE.

Methods Direct bisulfite-polymerase chain reaction (PCR) sequencing was performed to detect the HDAC6 promoter methylation in 33 patients with SLE and 35 controls healthy controls. The HDAC6 mRNA expression was measured in 93 SLE patients and 84 healthy controls by using the method of quantitative real-time PCR.

Results The methylation rates at HDAC6 -1293, -1273, and -1271, which were the binding sites of transcription factors, were significantly increased in the SLE patients compared with the healthy controls (p=0.041, 0.034, and 0.029, respectively). The SLE patients also have lower HDAC6 mRNA expression than the controls (p=0.031). However, there was no significant difference in HDAC6 mRNA expression between active and inactive SLE patients.

Conclusions The SLE patients have higher methylation in HDAC6 promoter and lower HDAC6 mRNA expression than the controls. These changes may be related to the susceptibility of SLE. However, they are not associated with the disease activity of SLE.

References

  1. Valenzuela-Fernandez, A., J. R. Cabrero, et al. HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions. Trends Cell Biol 2008; 18: 291-297.

  2. Liu CC, Ou TT, Wu CC, et al. Global DNA methylation, DNMT1, and MBD2 in patients with systemic lupus erythematosus. Lupus 2011; 20; 131-6

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.2641

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