Mirinezhad Mohammad Reza, Aghsizadeh Maliheh, Fazl Mashhadi Mohammadreza, Moazedi Sara, Mohammadi Bajgiran Maryam, Ghazizadeh Hamideh, Yaghouti Shayan, Mohammadian Ghosooni Mahdi, Mohammadi Mohammad Amin, Hasanzadeh Elahe, Ebrahimi Dabagh Ali, Rastegarmoghadam Ebrahimian Arezoo, Akbarpour Ensieh, Esmaily Habibollah, Ferns Gordon A, Hamzehloei Tayebeh, Pasdar Alireza, Ghayour-Mobarhan Majid
Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran.
Int J Fertil Steril. 2024 Feb 2;18(2):100-107. doi: 10.22074/ijfs.2023.560209.1365.
Premature menopause (PM) is the cessation of ovarian function before age 40. PM women are more likely to have cardiovascular diseases (CVDs), diabetes, and mental disorders. This is the first study that assessed the association of single nucleotide polymorphisms (SNPs) with anti-heat shock protein 27 (Hsp27), High-sensitivity C-reactive protein (hs- CRP), and PM and serum pro-oxidant-antioxidant balance (PAB), as putative risk factors for CVDs. We aimed to explore the association of oxidative stress markers with eight different SNPs shown to be related to premature menopause.
In this cross-sectional research, we included 183 healthy women and 117 premature menopausal women. We determined baseline characteristics for all participants and measured serum hs-CRP, anti-HSP-27 antibody titer, and PAB levels using the established methods. Genotyping for eight SNPs was done using the tetra amplification refractory mutation system polymerase chain reaction (Tetra-ARMS PCR) and allele-specific oligonucleotide PCR (ASO-PCR) methods.
We found a significant difference between mean serum PAB levels and the genetic variant of rs16991615 (P=0.03). ANCOVA showed a significant effect of the genotypes rs4806660 and rs10183486 on hs-CRP serum levels in the case and control groups, respectively (P=0.04 and P=0.007). ANCOVA also showed an association between rs244715 genotypes and anti-hsp27 serum levels in the case group (P=0.02). There was a significant effect of the genotypes of rs451417 on the serum hs-CRP level in the control group (P=0.03).
There was a significant association of the genetic variants related to PM with oxidative stress and inflammatory markers (serum PAB, anti-hsp27 antibody, and hs-CRP). Accordingly, this seems to be an effective approach to predicting susceptible subjects for cardiovascular and mental disorders as well as various cancers.
过早绝经(PM)是指40岁之前卵巢功能的停止。过早绝经的女性更易患心血管疾病(CVD)、糖尿病和精神障碍。这是第一项评估单核苷酸多态性(SNP)与抗热休克蛋白27(Hsp27)、高敏C反应蛋白(hs-CRP)、过早绝经以及血清促氧化剂-抗氧化剂平衡(PAB)之间关联的研究,这些因素被认为是心血管疾病的潜在危险因素。我们旨在探究氧化应激标志物与八个已显示与过早绝经相关的不同SNP之间的关联。
在这项横断面研究中,我们纳入了183名健康女性和117名过早绝经女性。我们确定了所有参与者的基线特征,并使用既定方法测量血清hs-CRP、抗HSP-27抗体滴度和PAB水平。使用四重扩增不应性突变系统聚合酶链反应(Tetra-ARMS PCR)和等位基因特异性寡核苷酸PCR(ASO-PCR)方法对八个SNP进行基因分型。
我们发现rs16991615的基因变异与血清PAB平均水平之间存在显著差异(P = 0.03)。协方差分析显示,rs4806660和rs10183486基因型分别对病例组和对照组的hs-CRP血清水平有显著影响(P = 0.04和P = 0.007)。协方差分析还显示,rs244715基因型与病例组的抗hsp27血清水平之间存在关联(P = 0.02)。rs451417基因型对对照组的血清hs-CRP水平有显著影响(P = 0.03)。
与过早绝经相关的基因变异与氧化应激和炎症标志物(血清PAB、抗hsp27抗体和hs-CRP)之间存在显著关联。因此,这似乎是预测心血管和精神障碍以及各种癌症易感人群的有效方法。