背景:多囊卵巢综合征(PCOS)是一种普遍存在的内分泌疾病,影响全球育龄妇女的大量人口。无数复杂的相互交织的因素,从病因,遗传,和表观遗传原因导致这种疾病。在不同的因素中,维生素D对多囊卵巢综合征(PCOS)女性的健康和生育能力至关重要。维生素D受体(VDR)促进了维生素D的重要性,类固醇/甲状腺激素受体超家族中的一个配体依赖性转录因子,控制维生素D的多效性生物学特性。
目的:本研究的目的是评估VDR基因启动子甲基化的作用,一种具有许多生物学用途的转录因子,其相对表达与临床病理结果和结果。
方法:共采集200份血样,100名来自PCOS病例受试者,正常健康对照组分别为100名,通过qRT-PCR评估以确定表达总结。MS-PCR技术用于分析VDR基因的启动子甲基化状态。抽取血样,分别,对于每种情况,对照研究分别针对给定研究的不同阶段进行实验,其中维生素D的估计也是其中的一部分。
结果:在这项测试与对照研究中,首先,发现VDR基因的启动子甲基化状态更为突出,即,在84例(84%)中发现了VDR基因的超甲基化,在正常的健康对照中,已发现(62%)。VDR基因的启动子甲基化状态具有显著差异(p值<0.0001*)。第二,通过平均倍数变化0.8743(±0.06466)(p值0.0054**),发现大多数(64%)PCOS病例样本中VDR基因的表达强烈下调.这个结果是,因此,指示VDR基因在PCOS发病机制中的作用,因为所述基因下调。此外,与维生素D参数相比,发现VDR启动子基因的高甲基化和表达分析与PCOS相关。某些病例和对照研究分析显示,维生素D水平正常的患者对PCOS的指示作用较小,反之亦然。
结论:我们的研究,是克什米尔独有的,VDR证实了PCOS中的异常甲基化构型,随后基因表达下调,即根据我们的PCOS病例对对照研究的结论,VDR基因表达(下调)和甲基化状态(高甲基化)之间呈负相关.
Polycystic ovarian syndrome (PCOS) is a prevailing endocrinopathy affecting a significant population of women of reproductive age across the globe. A myriad set of complex intertwined factors ranging from etiological, genetic, and epigenetic reasons cause this disorder. Out of the different factors, vitamin D shows an imperative aspect in health and fertility of women with polycystic ovary syndrome (PCOS). The importance of vitamin D is facilitated by vitamin D receptor (VDR), a ligand-dependent transcription factor in the steroid/ thyroid hormone receptor superfamily that controls the pleiotropic biological properties of vitamin D.
The purpose of this study was to evaluate the role of promoter methylation of the VDR gene, a transcription factor with numerous biological utilities, with its relative expression and clinico-pathological findings and outcomes.
A total of 200 blood samples were collected, 100 from PCOS case subjects, and 100 from the normal healthy controls respectively, which were assessed by qRT-PCR for determining the expression summary. MS-PCR technique was used for analyzing the promoter methylation status of the VDR gene. Blood samples were withdrawn, respectively, for each case and the control
study separately experimented for different stages for the given
study, of which estimation of vitamin D was also a part.
In this test-versus-control
study, first, the promoter methylation status of VDR gene was identified which was found more prominent i.e., hyper-methylation of the VDR gene was identified in 84 cases (84%), and in the normal healthy controls, it was found (62%). The promoter methylation status of the VDR gene has remarkably shown the results with a significant difference (p value < 0.0001*). Second, the expression analysis of VDR gene was found to be strongly downregulated in majority (64%) of PCOS case samples analyzed by means fold change of 0.8743 (± 0.06466) (p value 0.0054**). This result is, therefore, indicative of VDR gene role in PCOS pathogenesis as the said gene is downregulated. Moreover, compared to the vitamin D parameter, hyper-methylation and expression analysis of the VDR promoter gene were found to correspond to some associations with PCOS. Certain case-and-control
study analyses showed that patients with normal vitamin D levels showed less indicative effects of PCOS and vice versa.
Our
study, being exclusive from Kashmir, one of the foremost specified that VDR confirms anomalous methylation configuration in PCOS with subsequent downregulation in the gene expression i.e., there is an inverse correlation among VDR gene expression (downregulated) and methylation status (hyper-methylated) from the conclusion of our PCOS case-versus-control study.