目的:使用新的国际循证指南诊断的PCOS女性是否存在甲基化改变?
结论:在PCOS患者和健康对照中共发现264个差异甲基化探针(DMPs)和53个差异甲基化区域(DMRs)。
背景:PCOS是育龄妇女中常见的内分泌疾病,多囊卵巢形态学(PCOM)是该病的主要特征之一。由于有更灵敏的超声波机器,根据鹿特丹标准(每个卵巢≥12个腔卵泡)对PCOM的传统诊断目前存在争议,因为存在过度诊断的风险.新的国际循证指南将PCOM的阈值设定为每个卵巢≥20个窦卵泡,当使用频率带宽包括8MHz的阴道超声换能器时。然而,目前PCOS的DNA甲基化研究仍基于鹿特丹标准。这项研究旨在根据新的循证指南探索诊断为PCOS患者的DNA异常甲基化。
方法:这项横断面病例对照研究包括34例使用新的国际循证指南诊断的PCOS病例和36例对照。
方法:共有70名妇女,包括34例PCOS病例和36例对照,被招募。使用阵列技术对从参与者的全血样本中提取的DNA进行剖析。数据质量控制,预处理,注释,并进行统计分析。采用最小绝对收缩和选择算子(LASSO)回归建立具有DNA甲基化位点的PCOS诊断模型。
结果:我们确定了PCOS病例和对照组之间的264个DMPs,它们主要位于基因组的基因间区域或基因体,CpG公海站点,和功能元件的异染色质。途径富集剖析显示DMPs在介入甘油三酯调控的生物进程中显著富集。这些DMPs中的三个与PCOS易感基因甲状腺腺瘤相关蛋白(THADA)重叠,氨基肽酶O(AOEP),和三方基序家族样蛋白2(TRIML2)。鉴定了53个DMRs,它们的注释基因在同种异体移植排斥反应中大量富集,甲状腺激素的产生,和外围下游信号效应。两个DMRs与PCOS易感基因密切相关,钾电压门控通道亚家族A成员4(KCNA4)和法尼基-二磷酸法尼基转移酶1(FDFT1)。最后,基于LASSO回归,我们建立了一个用于PCOS诊断的高准确度甲基化标记模型(AUC=0.952)。
结论:研究队列是单中心的,样本量相对有限。需要对更多参与者进行进一步分析。
结论:这是第一项使用新的国际循证指南鉴定PCOS女性DNA甲基化改变的研究。它为新指南的应用提供了新的分子见解。
背景:本研究得到了国家重点研究发展计划(2021YFC2700400)的支持,国家自然科学基金基础科学中心项目(31988101),CAMS医学创新基金(2021-I2M-5-001),国家自然科学基金(32370916,82071606,82101707,82192874,31871509),山东省重点研发计划(2020ZLYS02),山东省泰山学者计划(ts20190988),山东大学基础研究经费。作者声明没有利益冲突。
背景:不适用。
OBJECTIVE: Is there any methylome alteration in women with PCOS who were diagnosed using the new international evidence-based
guidelines?
CONCLUSIONS: A total of 264 differentially methylated probes (DMPs) and 53 differentially methylated regions (DMRs) were identified in patients with PCOS and healthy controls.
BACKGROUND: PCOS is a common endocrine disorder among women of reproductive age and polycystic ovarian morphology (PCOM) is one of the main features of the disease. Owing to the availability of more sensitive ultrasound machines, the traditional diagnosis of PCOM according to the Rotterdam criteria (≥12 antral follicles per ovary) is currently debated as there is a risk of overdiagnosis. The new international evidence-based
guidelines set the threshold for PCOM as ≥20 antral follicles per ovary when using endovaginal ultrasound transducers with a frequency bandwidth that includes 8 MHz. However, current DNA methylation studies in PCOS are still based on the Rotterdam criteria. This study aimed to explore aberrant DNA methylation in patients diagnosed with PCOS according to the new evidence-based
guidelines.
METHODS: This cross-sectional case-control study included 34 PCOS cases diagnosed using new international evidence-based guidelines and 36 controls.
METHODS: A total of 70 women, including 34 PCOS cases and 36 controls, were recruited. DNA extracted from whole blood samples of participants were profiled using array technology. Data quality control, preprocessing, annotation, and statistical analyses were performed. Least absolute shrinkage and selection operator (LASSO) regression were used to build a PCOS diagnosis model with DNA methylation sites.
RESULTS: We identified 264 DMPs between PCOS cases and controls, which were mainly located in intergenic regions or gene bodies of the genome, CpG open sea sites, and heterochromatin of functional elements. Pathway enrichment analysis showed that DMPs were significantly enriched in biological processes involved in triglyceride regulation. Three of these DMPs overlapped with the PCOS susceptibility genes thyroid adenoma-associated protein (THADA), aminopeptidase O (AOPEP), and tripartite motif family-like protein 2 (TRIML2). Fifty-three DMRs were identified and their annotated genes were largely enriched in allograft rejection, thyroid hormone production, and peripheral downstream signaling effects. Two DMRs were closely related to the PCOS susceptibility genes, potassium voltage-gated channel subfamily A member 4 (KCNA4) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1). Finally, based on LASSO regression, we built a methylation marker model with high accuracy for PCOS diagnosis (AUC=0.952).
CONCLUSIONS: The study cohort was single-center and the sample size was relatively limited. Further analyses with a larger number of participants are required.
CONCLUSIONS: This is the first study to identify DNA methylation alterations in women with PCOS diagnosed using the new international evidence-based
guideline, and it provided new molecular insight into the application of the new
guidelines.
BACKGROUND: This study was supported by the National Key Research and Development Program of China (2021YFC2700400), Basic Science Center Program of NSFC (31988101), CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), National Natural Science Foundation of China (32370916, 82071606, 82101707, 82192874, and 31871509), Shandong Provincial Key Research and Development Program (2020ZLYS02), Taishan Scholars Program of Shandong Province (ts20190988), and Fundamental Research Funds of Shandong University. The authors declare no conflicts of interest.
BACKGROUND: N/A.