Hu Ya-Fen, Hua Lin, Tuo Xiu, Shi Ting-Ting, Yang Yi-Lin, Liu Yun-Fu, Yan Zhong-Yu, Xin Zhong
Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Department of Endocrinology, The People's Hospital of Daxing District, Beijing, China.
Endocr Connect. 2020 Jul;9(7):617-626. doi: 10.1530/EC-20-0147.
The pathogenesis underlying the alterations of orbital architecture in Graves' orbitopathy (GO) is not yet fully understood. The present study aimed to investigate the association of DNA methylation in peripheral blood and orbital volumetry in Chinese patients with GO.
A total of 35 GO subjects (70 orbits) were subjected to CT scan. The total cross-sectional area of the extraocular muscles (orbital muscles, OM), total orbit area (TOA), and the exophthalmometry were measured and OM/TOA ratio was calculated. Targeted bisulfite sequencing was performed on seven candidate genes.
No significant correlation was established between the DNA methylation levels of these genes and exophthalmometry. The MBP methylation level was found to be correlated with OM/TOA ratio (P < 0.05). Multiple linear regression analysis on parameters including age, sex, TRAb, duration of GO, and DNA methylation levels of seven genes with OM/TOA ratio confirmed that MBP and OM/TOA ratio had a significant correlation (P < 0.05). The partial least squares analysis showed that the top three genes with the highest loadings were MBP, BOLL, and BECN1 and that OM/TOA ratio affected the DNA methylation block than exophthalmometry.
This study provided preliminary evidence that MBP is a potential gene associated with OM enlargement in GO patients according to the combination of DNA methylation sequencing and orbital CT measurement.
格雷夫斯眼病（GO）眼眶结构改变的发病机制尚未完全明确。本研究旨在探讨中国GO患者外周血DNA甲基化与眼眶容积测定之间的关联。
对35例GO患者（70只眼眶）进行CT扫描。测量眼外肌（眼眶肌肉，OM）的总横截面积、总眼眶面积（TOA）和眼球突出度，并计算OM/TOA比值。对7个候选基因进行靶向亚硫酸氢盐测序。
这些基因的DNA甲基化水平与眼球突出度之间未建立显著相关性。发现髓鞘碱性蛋白（MBP）甲基化水平与OM/TOA比值相关（P < 0.05）。对年龄、性别、促甲状腺素受体抗体（TRAb）、GO病程以及7个基因的DNA甲基化水平与OM/TOA比值等参数进行多元线性回归分析，证实MBP与OM/TOA比值具有显著相关性（P < 0.05）。偏最小二乘分析显示，载荷最高的前三个基因是MBP、布林蛋白（BOLL）和自噬相关蛋白1（BECN1），且OM/TOA比值比眼球突出度对DNA甲基化模块的影响更大。
本研究通过DNA甲基化测序与眼眶CT测量相结合，初步证明MBP是GO患者眼眶肌肉增大的潜在相关基因。
