目的:HNF1α转录因子调节参与β细胞发育的基因网络,并作为胰腺β细胞转录缺陷的模型;该基因的突变导致MODY。这项研究的目的是评估最常见的MODY引起基因的启动子甲基化和表达谱,HNF1α,在克什米尔MODY患者中,作为导致葡萄糖失调的因素,因为以前没有对克什米尔的MODY患者进行过此类研究。
方法:该研究包括85名克什米尔受试者。使用标准方案提取样品的DNA和RNA。HNF1α启动子甲基化谱通过DNA的亚硫酸氢盐转化和MSP来评估,而qPCR用于表达分析。
结果:在大多数MODY(60%)和T1D(72%)病例(p值0.0349*)中发现HNF1α的表达上调(p值0.0349*)。在具有高甲基化HNF1α启动子的MODY病例中,HNF1α表达高1.33倍(p值0.0360*)。HbA1c水平>7%的MODY患者HNF1α表达上调2.3倍(p值0.0025**)。FBS水平>7.7mmol/l的MODY病例比FBS水平≤7.7mmol/l的MODY病例上调0.646倍(p值0.0161*)。
结论:在这项研究中,我们发现随着葡萄糖失调的进展,血液FBS,苏格兰皇家银行,和HbA1c水平上升,在更高的层次上,HNF1α表达也升高。从获得的结果来看,我们可以得出结论,HNF1α在MODY中强烈上调,从而表明HNF1α基因过表达对葡萄糖调节的有害作用。
OBJECTIVE: HNF1α transcription factor regulates a network of genes involved in the development of β-cells and also serves as a model for transcription defects in pancreatic β-cells; mutations in this gene cause MODY. The goal of this study was to assess the promoter methylation and expression profile of the most common MODY causing gene,
HNF1α, in Kashmiri MODY patients, as factors responsible for glucose dysregulation, as no such study had been performed on MODY patients in Kashmir previously.
METHODS: The study included 85 Kashmiri subjects. Samples were extracted for DNA and RNA using standard protocols. The HNF1α promoter methylation profile was assessed by bisulfite conversion of the DNA followed by MSP, whereas qPCR was used for expression analysis.
RESULTS: The expression of
HNF1α was found to be upregulated (p value 0.0349*) in majority of MODY (60%) and T1D (72%) cases (p value 0.0349*).
HNF1α expression was 1.33-fold higher in MODY cases with hypermethylated
HNF1α promoters (p value 0.0360*). HNF1α expression was upregulated by 2.3-fold in MODY patients with HbA1c levels > 7% (p value 0.0025**). MODY cases with FBS levels > 7.7 mmol/l were upregulated by 0.646-fold than those with FBS levels ≤ 7.7 mmol/l (p value 0.0161*).
CONCLUSIONS: In this study, we found that as glucose dysregulation progresses, blood FBS, RBS, and HbA1c levels rise, and that at higher levels, HNF1α expression rises as well. From the results obtained, we may conclude that HNF1α is strongly upregulated in MODY, thus indicating the deleterious effect of over expression of
HNF1α gene on glucose regulation.