线粒体 DNA 拷贝数和变异与多囊卵巢综合征临床特征的关系。

IF 3.8 3区 医学 Q2 CELL BIOLOGY Molecular and Cellular Endocrinology Pub Date : 2024-10-18 DOI:10.1016/j.mce.2024.112386
Samia Palat Tharayil , Sayli Rasal , Ulka Gawde , Srabani Mukherjee , Anushree Patil , Beena Joshi , Susan Idicula-Thomas , Pallavi Shukla
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引用次数: 0

摘要

越来越多的证据表明,线粒体功能障碍是导致多囊卵巢综合症发病机制的一个新因素。在此,我们分析了多囊卵巢综合征女性和非多囊卵巢综合征女性患者的线粒体功能生物标志物--mtDNA拷贝数,并研究了其与临床特征的相关性。在本研究中,我们进一步分析了我们之前报告的 383 个 mtDNA 变异与多囊卵巢综合征特征的相关性,并对变异蛋白进行了结构分析。我们的研究结果表明,与非多囊卵巢综合征组相比,多囊卵巢综合征妇女的线粒体DNA(mtDNA)相对拷贝数明显减少,且与腰臀比(WHR)、甘油三酯显著成反比,与高密度脂蛋白胆固醇(HDL-C)成正比。在对多囊卵巢综合征组的年龄进行调整后,观察到 mtDNA 拷贝数与 WHR 呈显著负相关。无监督分层聚类分析显示,12556G、1488T、9200G、9670G、3308G、14480G、15914T 和 5426G 等罕见的低异质 mtDNA 变异与多囊卵巢综合征相关性状密切相关。在这些变异中,ND5 基因的变异 12256G 既影响蛋白质结构的灵活性,也影响其整体稳定性。这项研究首次揭示了多囊卵巢综合征妇女的 mtDNA 拷贝数与 WHR 的显著相关性,表明线粒体功能障碍与多囊卵巢综合征的中心性肥胖之间存在联系。我们还首次发现了罕见的 mtDNA 变异与多囊卵巢综合征特征的相关性,凸显了罕见 mtDNA 变异的临床意义,这些变异可作为多囊卵巢综合征及其相关合并症风险的早期预测因子,有助于多囊卵巢综合征的治疗。
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Relation of mitochondrial DNA copy number and variants with the clinical characteristics of polycystic ovary syndrome
Mounting evidences suggests mitochondrial dysfunction as a novel contributor in the pathogenesis of PCOS. Herein, we analyzed mtDNA copy number, a biomarker of mitochondrial function in women with PCOS and non-PCOS participants and study its correlation with their clinical characteristics. In this study, we further analyzed association of 383 mtDNA variants, as reported previously by us, with characteristic traits of PCOS and perform structural analysis of mutated protein. Our results indicate relative mitochondrial DNA (mtDNA) copy number to be significantly reduced in women with PCOS compared to non-PCOS group and significantly inversely related to waist to hip ratio (WHR), triglycerides and positively related to high density lipoprotein-cholesterol (HDL-C). After adjustment of the age in the PCOS group, significantly negative correlation of mtDNA copy number with WHR was observed. Unsupervised hierarchical clustering analysis revealed rare, low heteroplasmic mtDNA variants such as 12556G, 1488T, 9200G, 9670G, 3308G, 14480G, 15914T and 5426G to be strongly associated with PCOS related traits. Among these variants, variant 12256G in ND5 gene affected both the flexibility and overall stability of the protein structure. This study is first to reveal significant correlation of mtDNA copy number with WHR in women with PCOS indicating link between mitochondrial dysfunction with central obesity in PCOS. we also first time showed association of rare mtDNA variants with characteristics traits of PCOS highlighting the clinical significance of rare mtDNA variants, which may cumulatively act as early predictors of risk of PCOS and its related comorbidities which may help in the management of PCOS.
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来源期刊
Molecular and Cellular Endocrinology
Molecular and Cellular Endocrinology 医学-内分泌学与代谢
CiteScore
9.00
自引率
2.40%
发文量
174
审稿时长
42 days
期刊介绍: Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.
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