Chinese Medical Sciences Journal ›› 2022, Vol. 37 ›› Issue (1): 52-59.doi: 10.24920/003953

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  1. 1陕西中医药大学公共卫生学院,陕西 咸阳 712046,中国
    2西安交通大学医学部公共卫生学院地方病研究所,国家卫健委微量元素与地方病重点实验室,西安 710061,中国
  • 收稿日期:2021-06-10 接受日期:2021-12-17 出版日期:2022-03-31 发布日期:2022-03-01
  • 通讯作者: 熊咏民

Crosstalk between CpG Methylation and Polymorphisms (CpG-SNPs) in the Promotor Region of DIO2 in Kashin-Beck Disease

Rongqiang Zhang1,2,Dandan Zhang2,Di Zhang2,Xiaoli Yang2,Qiang Li2,Chen Wang2,Xuena Yang2,Yongmin Xiong2,*()   

  1. 1School of Public Health, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, China
    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
  • Received:2021-06-10 Accepted:2021-12-17 Published:2022-03-31 Online:2022-03-01
  • Contact: Yongmin Xiong


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。

关键词: 大骨节病, DNA甲基化, CpG位点, CpG-SNP


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.

Key words: Kashin-Beck disease, DNA methylation, CpG, CpG-SNP

基金资助: 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)

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