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CD3Z hypermethylation is associated with severe clinical manifestations in systemic lupus erythematosus and reduces CD3?-chain expression in T cells.


ABSTRACT: The importance of hypomethylation in SLE is well recognized; however, the significance of hypermethylation has not been well characterized. We screened hypermethylated marks in SLE and investigated their possible implications.DNA methylation marks were screened in SLE whole-blood DNA by microarray, and two marks ( CD3Z and VHL hypermethylations) were confirmed by a methylation single-base extension method in two independent ethnic cohorts consisting of 207 SLE patients and 151 controls. The correlation with clinical manifestations and the genetic influence on those epigenetic marks were analysed.Two epigenetic marks, CD3Z and VHL hypermethylation, were significantly correlated with SLE: CD3Z hypermethylation (odds ratio = 7.76; P = 1.71 × 10 -13 ) and VHL hypermethylation (odds ratio = 3.77; P = 3.20 × 10 -8 ), and the increased CD3Z methylation was correlated with downregulation of the CD3?-chain in SLE T cells. In addition, less genetic influence on CD3Z methylation relative to VHL methylation was found in analyses of longitudinal and twin samples. Furthermore, a higher CD3Z methylation level was significantly correlated with a higher SLE disease activity index and more severe clinical manifestations, such as proteinuria, haemolytic anaemia and thrombocytopenia, whereas VHL hypermethylation was not.CD3Z hypermethylation is an SLE risk factor that can be modified by environmental factors and is associated with more severe SLE clinical manifestations, which are related to deranged T cell function by downregulating the CD3?-chain.

SUBMITTER: Hong KM 

PROVIDER: S-EPMC5850282 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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CD3Z hypermethylation is associated with severe clinical manifestations in systemic lupus erythematosus and reduces CD3ζ-chain expression in T cells.

Hong Kyeong-Man KM   Kim Hyun-Kyoung HK   Park Seong-Yeol SY   Poojan Shiv S   Kim Mi-Kyung MK   Sung Joohon J   Tsao Betty P BP   Grossman Jennifer M JM   Rullo Ornella J OJ   Woo Jennifer M P JM   McCurdy Deborah K DK   Rider Lisa G LG   Miller Frederick W FW   Song Yeong-Wook YW  

Rheumatology (Oxford, England) 20170301 3


<h4>Objective</h4>The importance of hypomethylation in SLE is well recognized; however, the significance of hypermethylation has not been well characterized. We screened hypermethylated marks in SLE and investigated their possible implications.<h4>Methods</h4>DNA methylation marks were screened in SLE whole-blood DNA by microarray, and two marks ( CD3Z and VHL hypermethylations) were confirmed by a methylation single-base extension method in two independent ethnic cohorts consisting of 207 SLE p  ...[more]

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