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硒蛋白基因DIO2启动子区CpG甲基化与CpG-SNPs的交互作用对大骨节病的影响
- Affiliations：
1. 1School of Public Health, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, China
2. 2Institute of Endemic Diseases and Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People’s Republic of China, School of Public Health, Xi′an Jiaotong University Health Science Center, Xi′an 710061, China
- Author bio：
*E-mail: xiongym@mail.xjtu.edu.cn.
- Funds：国家自然科学基金(82073494);陕西省重点研发计划(2020SF-076);中国富硒产业研究院富硒产业全产业链专项研发计划项目(2020FXZX0501);陕西中医药大学重点创新团队(132041933)
DOI：10.24920/003953
中图分类号：收稿日期：2021-06-10，
录用日期：2021-12-17，
网络出版日期：2022-03-01，
纸质出版日期：2022-03-31
- Accepted：
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张荣强, 张丹丹, 张迪, 等. 硒蛋白基因DIO2启动子区CpG甲基化与CpG-SNPs的交互作用对大骨节病的影响[J]. 中国医学科学杂志（英文版）, 2022,37(1):52-59.
Zhang Rongqiang, Zhang Dandan, Zhang Di, et al. Crosstalk between CpG Methylation and Polymorphisms (CpG-SNPs) in the Promotor Region of
DIO2 in Kashin-Beck Disease[J]. Chinese medical sciences journal, 2022, 37(1): 52-59.张荣强, 张丹丹, 张迪, 等. 硒蛋白基因DIO2启动子区CpG甲基化与CpG-SNPs的交互作用对大骨节病的影响[J]. 中国医学科学杂志（英文版）, 2022,37(1):52-59. DOI： 10.24920/003953.
Zhang Rongqiang, Zhang Dandan, Zhang Di, et al. Crosstalk between CpG Methylation and Polymorphisms (CpG-SNPs) in the Promotor Region of
DIO2 in Kashin-Beck Disease[J]. Chinese medical sciences journal, 2022, 37(1): 52-59. DOI： 10.24920/003953.
摘要
目的
本研究旨在明确大骨节病（KBD）患者硒蛋白
DIO2
基因启动子区4个CpGs的甲基化水平和2个CpG-SNPs的基因型
并探讨两者的相关性。
方法
采用基质辅助激光解吸电离飞行时间质谱技术（MALDI-TOF-MS）检测KBD患者（n=16）和健康对照组（n=16）血液中
DIO2
基因启动子区的4个CpGs和2个CpG-SNPs
分析比较两组及不同CpG-SNP基因型KBD患者CpGs甲基化水平。
结果
KBD患者全血中
DIO2
mRNA水平明显低于健康对照组（
P
<
0.05）
KBD患者DIO2-1_CpG_3甲基化水平明显高于健康对照组（
P
<
0.05）
4个CpGs的甲基化水平在KBD患者和健康对照组无明显差异（
P
>
0.05）
GA/AA基因型（DIO2 rs955849187）KBD患者DIO2启动子区DIO2-1_CpG_3甲基化水平显著高于GG基因型KBD患者（
P
<
0.05）。
结论
KBD患者
DIO2
启动子区甲基化水平升高
CpG-SNPs DIO2 rs955849187变异基因型的KBD患者
DIO2
启动子区甲基化水平亦呈升高趋势。
Abstract
Objective
This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of
DIO2
in patients with Kashin-Beck disease (KBD). We also analyzed the interaction between the CpGs methylations and CpG-SNPs.
Methods
Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects. Four CpGs and two CpG-SNPs in the promoter regions of
DIO2
were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The CpGs methylation levels were compared between samples from KBD patients and healthy subjects. The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes.
Results
The mRNA expression of
DIO2
in whole blood of KBD patients was significnatly lower than in healthy controls (
P
<
0.05). The methylation levels of
DIO2
-1_CpG_3 in KBD patients were significantly higher than those in healthy controls (
P
<
0.05). The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls. The methylation level of
DIO2
-1_CpG_3 in the promoter region of
DIO2
in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype (
P
<
0.05).
Conclusion
The methylation level of
DIO2
increases in KBD patients. Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs
DIO2
rs955849187.
关键词
Keywords
references
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