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围绝经期高血压女性HV1和HV2区域线粒体DNA多态性及12S核糖体RNA研究

Mitochondrial DNA Polymorphism in HV1 and HV2 Regions and 12S rDNA in Perimenopausal Hypertensive Women.

作者信息

Kwaśniewski Wojciech, Stupak Aleksandra, Warowicka Alicja, Goździcka-Józefiak Anna, Mosiewicz Jerzy, Mieczkowska Jolanta

机构信息

Gynecology and Oncological Gynecology Department, Medical University of Lublin, 20-081 Lublin, Poland.

Obstetrics and Pregnancy Pathology Department, Medical University of Lublin, 20-081 Lublin, Poland.

出版信息

Biomedicines. 2023 Mar 8;11(3):823. doi: 10.3390/biomedicines11030823.

Abstract

Estrogens enhance cellular mitochondrial activity. The diminution of female hormones during menopause may have an effect on the mitochondrial genome and the expression of mitochondrial proteins. Hence, oxidative stress and the pro-inflammatory state contribute to the formation of systemic illnesses including arterial hypertension (AH). This study aimed to determine the types and frequency of mutations in the mitochondrial DNA (mtDNA) nucleotide sequence in the hypervariable regions 1 and 2 (HV1 and HV2) and the 12S RNA coding sequence of the D-loop in postmenopausal women with hypertension. In our study, 100 women were investigated, 53 of whom were postmenopausal and 47 of whom were premenopausal (53.9 ± 3.7 years vs. 47.7 ± 4.2 years, respectively). Of those studied, 35 premenopausal and 40 postmenopausal women were diagnosed with AH. A medical checkup with 24 h monitoring of blood pressure (RR) and heart rate was undertaken (HR). The polymorphism of the D-loop and 12S rDNA region of mtDNA was examined. Changes in the nucleotide sequence of mtDNA were observed in 23% of the group of 100 women. The changes were identified in 91.3% of HV1 and HV2 regions, 60.9% of HV1 segments, 47.5% of HV2 regions, and 43.5% of 12S rDNA regions. The frequency of nucleotide sequence alterations in mtDNA was substantially higher in postmenopausal women (34%) than in premenopausal women (10.6%), = 0.016. A higher frequency of changes in HV1 + HV2 sections in postmenopausal women (30.2%) compared to the premenopausal group (10.6%) was detected, = 0.011. Only postmenopausal women were found to have modifications to the HV2 segment and the 12S rDNA region. After menopause, polymorphism in the mtDNA region was substantially more frequent in women with arterial hypertension than before menopause ( = 0.030; 37.5% vs. 11.5%). Comparable findings were observed in the HV2 and HV1 regions of the AH group (35% vs. 11.5%), = 0.015, in the HV1 segment (25% vs. 11.5%), = 0.529, and in the HV2 segment, 12S rDNA (25% vs. 0%). More than 80% of all changes in nucleotide sequence were homoplasmic. The mtDNA polymorphisms of the nucleotide sequence in the HV1 and HV2 regions, the HV2 region alone, and the 12S RNA coding sequence were associated with estrogen deficiency and a more severe course of arterial hypertension, accompanied by symptoms of adrenergic stimulation.

摘要

雌激素可增强细胞线粒体活性。绝经期间女性激素的减少可能会影响线粒体基因组及线粒体蛋白的表达。因此,氧化应激和促炎状态会促使包括动脉高血压(AH)在内的全身性疾病的形成。本研究旨在确定绝经后高血压女性线粒体DNA(mtDNA)核苷酸序列在高变区1和2(HV1和HV2)以及D环的12S RNA编码序列中的突变类型和频率。在我们的研究中,对100名女性进行了调查,其中53名是绝经后女性,47名是绝经前女性(分别为53.9±3.7岁和47.7±4.2岁)。在这些研究对象中,35名绝经前女性和40名绝经后女性被诊断为动脉高血压。进行了24小时血压(RR)和心率(HR)监测的医学检查。检测了mtDNA的D环和12S rDNA区域的多态性。在100名女性组中,23%的人观察到mtDNA核苷酸序列发生变化。这些变化在HV1和HV2区域的91.3%、HV1片段的60.9%、HV2区域的47.5%以及12S rDNA区域的43.5%中被发现。绝经后女性mtDNA核苷酸序列改变的频率(34%)显著高于绝经前女性(10.6%),P = 0.016。检测到绝经后女性HV1 + HV2区域变化的频率(30.2%)高于绝经前组(10.6%),P = 0.011。仅在绝经后女性中发现HV2片段和12S rDNA区域有改变。绝经后,动脉高血压女性mtDNA区域的多态性比绝经前明显更频繁(P = 0.030;37.5%对11.5%)。在动脉高血压组的HV2和HV1区域(35%对11.5%)、HV1片段(25%对11.5%)以及HV2片段、12S rDNA(25%对0%)中观察到类似结果。所有核苷酸序列变化中超过80%是同质性的。HV1和HV2区域、单独的HV2区域以及12S RNA编码序列的mtDNA核苷酸序列多态性与雌激素缺乏以及更严重的动脉高血压病程相关,并伴有肾上腺素能刺激症状。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dceb/10044999/31b9110cc7de/biomedicines-11-00823-g001.jpg

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