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A genome-wide DNA methylation analysis in peripheral blood from patients identifies risk loci associated with Graves' orbitopathy.

Abstract：

OBJECTIVE:Graves' orbitopathy (GO) is an inflammatory orbital disease of autoimmune origin with the potential to cause severe functional and psychosocial effects. The pathogenesis has not been fully elucidated. We investigated whether DNA methylation was associated with GO incidence in Chinese patients. MATERIALS AND METHODS:Six GO patients and six age-matched controls were recruited, and genome-wide DNA methylation patterns were analyzed in their peripheral blood. t tests were performed to determine differential methylated sites in genomic regions and the univariable logistic regression analyses was performed to evaluate their risk with GO incidence. Cluster analysis and principal component analysis (PCA) were performed to determine the effects of the extracted differentially methylated sites. RESULTS:One hundred and forty-eight differentially methylated sites were identified, including CD14 (fold change = 4.31, p = 0.005), IL17RE (fold change = 2.128, p = 0.005), and DRD4 (fold change = 0.25, p = 0.004), and were supported by cluster and PCA analyses. Univariable logistic regression analyses showed that the methylation patterns at 12 loci were associated with GO incidence. The relative risk per 1% decrease in methylation at ZCCHC6 and GLI3 was 0.15 (95% CI 0.03-0.91; p = 0.039) and 0.65 (95% CI 0.42-0.98; p = 0.042), respectively. Pearson correlation analyses demonstrated that methylation levels at IL17RE were positively associated with Clinical Activity Score (CAS) (r = 0.967, p < 0.05). CONCLUSIONS:Our results demonstrate that differential methylation levels at analyzed sites (genes) may be risk markers of GO. DNA methylation analysis could provide new insights into understanding the disease and provide new treatment strategies for GO in Chinese patients.

journal_name

J Endocrinol Invest

journal_title

Journal of endocrinological investigation

authors

Xin Z,Hua L,Shi TT,Tuo X,Yang FY,Li Y,Cao X,Yang JK

doi

10.1007/s40618-017-0796-6

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

719-727

issue

eissn

0391-4097

issn

1720-8386

pii

10.1007/s40618-017-0796-6

journal_volume

pub_type

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A genome-wide DNA methylation analysis in peripheral blood from patients identifies risk loci associated with Graves' orbitopathy.