天津医药

天津医药 ›› 2021, Vol. 49 ›› Issue (4): 406-409.doi: 10.11958/20202810

• 临床研究 • 上一篇    下一篇

新疆维吾尔族2型糖尿病FOSL2 DNA甲基化水平与胰岛素抵抗及胰岛β细胞分泌功能的关系#br#

侯泽鑫1,李军2,李思源2,曹国磊3,胡颖4   

  1. 1石河子大学医学院第一附属医院内分泌代谢科（邮编832000）；2石河子大学医学院组织学与胚胎学教研室；3新疆医科大学附属肿瘤医院呼吸神经内科；4新疆医科大学第四附属医院神志病科
  • 收稿日期:2020-10-14 修回日期:2020-12-09 出版日期:2021-04-15 发布日期:2021-04-16
  • 通讯作者: 李军 E-mail:xjlijun@163.com
  • 作者简介:侯泽鑫（1992），男，硕士在读，主要从事糖尿病与肿瘤关系的研究。E-mail：zexinhou@163.com
  • 基金资助:
    兵团区域创新引导计划（2018BB040）；石河子大学成果转化与技术推广项目（CGZH201911）

Relationship between FOSL2 DNA methylation level and insulin resistance and islet β cell secretion function in type 2 diabetes mellitus of Xinjiang Uygur nationality

HOU Ze-xin1, LI Si-yuan2, CAO Guo-lei3, HU Ying4, WANG Tong-yao1, LI Jun1△   

  1. 1 Department of Endocrinology and Metabolism, the First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi 832000, China; 2 Department of Histology and Embryology, School of Medicine, Shihezi University; 3 Department of Neurology and Respiratory Medicine, Tumor Hospital Affiliated to Xinjiang Medical University; 4 Department of 
    Psychiatry, the Fourth Affiliated Hospital of Xinjiang Medical University
  • Received:2020-10-14 Revised:2020-12-09 Published:2021-04-15 Online:2021-04-16
  • Contact: LI Jun E-mail:xjlijun@163.com

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摘要： 目的　探讨新疆维吾尔族2型糖尿病FOSL2 DNA甲基化水平与胰岛素抵抗及胰岛β细胞分泌功能的关系。方法　选取内分泌代谢科就诊的维吾尔族患者100例，其中正常对照组（NC组，n=50）及2型糖尿病组（T2DM组，n=50）。测定空腹血糖（FPG）、三酰甘油（TG）、空腹胰岛素（FINS）等生化指标，飞行时间质谱法（MALDI-TOF-MS）检测FOSL2 DNA甲基化水平，稳态模型评估胰岛素抵抗指数（HOMA-IR）等指标，Spearman法进行指标间相关性分析，多元逐步线性回归分析胰岛素抵抗及胰岛β细胞分泌功能的影响因素。结果　与NC组相比，T2DM组体质量指数（BMI）、FPG、糖化血红蛋白（HbA1c）、TG、低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、FINS、HOMA-IR升高，高密度脂蛋白胆固醇（HDL-C）、稳态模型胰岛素敏感指数（HOMA-ISI）、稳态模型胰岛β细胞功能（HOMA-β）降低；T2DM组8个胞嘧啶-鸟嘌呤二核苷酸（CpG）单元甲基化水平升高；相关性分析结果显示，FOSL2 DNA有6个CpG单元甲基化水平与HOMA-IR呈正相关，与HOMA-ISI呈负相关；有4个CpG单元甲基化水平与BMI呈正相关，与HOMA-β呈负相关；回归分析结果显示，CpG 12.13.14甲基化水平升高是HOMA-ISI、HOMA-β降低及HOMA-IR增高的影响因素，CpG 15.16.17甲基化水平升高是BMI增高的影响因素。结论　FOSL2可能通过DNA甲基化水平升高的方式参与维吾尔族T2DM胰岛素抵抗及胰岛β细胞分泌功能缺陷，从而导致T2DM的发生发展。

关键词: 糖尿病, 2型, 维吾尔族, DNA甲基化, FOSL2, 胰岛素抵抗

Abstract: Objective　To investigate the relationship between FOSL2 DNA methylation level and insulin resistance and islet β cell secretion function in type 2 diabetes mellitus of Xinjiang Uygur nationality. Methods　A total of 100 Uygur patients in the department of endocrinology and metabolism were selected as normal control group (NC group, n=50) and type 2 diabetes group (T2DM group, n=50). Biochemical indicators such as fasting plasma glucose (FPG), triglyceride (TG) and fasting serum insulin (FINS) were measured. DNA methylation level of FOSL2 was detected by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The homeostatic model assessment index of insulin resistance (HOMA-IR) was evaluated by steady-state model. The correlation between indicators was analyzed by Spearman method, and influencing factors of insulin resistance and the secretory function of pancreatic β cells were analyzed by multiple stepwise linear regression. Results　Compared with NC group, body mass index (BMI), FPG, glycosylated hemoglobin (HbA1c), low density lipoprotein cholesterol (LDL-C), TG, total cholesterol (TC), FINS and HOMA-IR increased and high density lipoprotein cholesterol (HDL-C), homeostatic model pancreatic β cell function (HOMA-β), homeostasis model insulin sensitivity index (HOMA-ISI) decreased in T2DM group. The methylation levels of 8 cytosine-phosphor-guanine (CpG) units were increased in the T2DM group. The results of correlation analysis showed that methylation levels of 6 CpG units in FOSL2 DNA were positively correlated with HOMA-IR and negatively correlated with HOMA-ISI. The methylation levels of 4 CpG units were positively correlated with BMI and negatively correlated with HOMA-β. The results of regression analysis showed that the increased methylation level of CpG 12.13.14 was the influencing factor for the decrease of HOMA-ISI, HOMA-β and the increase of HOMA-IR. The increased methylation level of CpG 15.16.17 was the influencing factor for the increase of BMI. Conclusion　FOSL2 may be involved in insulin resistance and pancreatic β cell secretion defect in Uyghur T2DM through the elevated DNA methylation level, thus leading to the occurrence and development of T2DM.

Key words: diabetes mellitus, type 2, UYGUR NATIONALITY, DNA methylation, FOSL2, insulin resistance

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