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

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

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-TOFMS)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,CpG12.13.14甲基化水平升高是HOMA-ISI、HOMA-β降低及HOMA-IR增高的影响因素,CpG15.16.17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。

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-phosphorguanine(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.