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髓过氧化物酶和基质金属蛋白酶-1组织抑制剂基因多态性及其与中国汉族人群子痫前期的关联。

Polymorphisms in myeloperoxidase and tissue inhibitor of metalloproteinase-1 genes and their association with preeclampsia in the Chinese Han population.

作者信息

Liu Li, He Dong, Zhou Weilin, Guo Zhiyang, Ma Yue, Liu Lingjie, He Hong, He Shuqi, Huang Yi

机构信息

Hospital of Stomatology, The First Affiliated Hospital, Clinical Research Platform for Interdiscipline, School of Stomatology, Jinan University, Guangzhou, 510630, China.

School of Basic Medical Sciences, Xiangnan University, Chenzhou, Hunan, 423000, China.

出版信息

Heliyon. 2024 Aug 23;10(17):e36685. doi: 10.1016/j.heliyon.2024.e36685. eCollection 2024 Sep 15.

Abstract

Hypertensive disorders of pregnancy (HDP) are multifaceted syndromes unique to pregnancy, characterized by increased blood pressure, edema, and proteinuria. Patients with HDP exhibit signs of endothelial dysfunction, possibly linked to increased myeloperoxidase (MPO) level and aberrant oxidative stress. Additionally, altered level of tissue inhibitor of metalloproteinase-1 (TIMP1) protein is associated with placental ischemia, hypoxia, and maternal vascular endothelial damage. Preeclampsia (PE) represents a critical stage of HDP that poses severe threats to maternal and fetal safety. This study aimed to determine the relationship between MPO and TIMP1 polymorphisms and the risk of PE in the Chinese Han population. Single nucleotide polymorphisms (SNPs), including MPO rs7208693, MPO rs2243828, and TIMP1 rs6609533, were genotyped in 170 patients with PE and 303 control participants. No significant association was observed between MPO polymorphisms (rs7208693 and rs2243828) and the risk of PE, whereas significant association between the TIMP1 rs6609533 A > G SNP and PE susceptibility was found. Specifically, individuals with the GG or AG genotypes had elevated risk of PE compared to those harboring the AA genotype. Furthermore, in the PE group, patients carrying the G allele were more likely to experience fetal growth restriction (FGR). In the non-PE group, the association between the G allele and the risk of FGR was not evident. In conclusion, the TIMP1 rs6609533 G allele in Chinese Han women was identified as a risk factor for PE. Our results indicated that the TIMP1 rs6609533 SNP can serve as a biomarker for the clinical diagnosis and treatment of PE.

摘要

妊娠期高血压疾病(HDP)是妊娠期特有的多方面综合征,其特征为血压升高、水肿和蛋白尿。HDP患者表现出内皮功能障碍的迹象,这可能与髓过氧化物酶(MPO)水平升高和异常氧化应激有关。此外,金属蛋白酶组织抑制剂-1(TIMP1)蛋白水平的改变与胎盘缺血、缺氧及母体血管内皮损伤有关。子痫前期(PE)是HDP的一个关键阶段,对母婴安全构成严重威胁。本研究旨在确定中国汉族人群中MPO和TIMP1基因多态性与PE风险之间的关系。对170例PE患者和303例对照参与者进行了基因分型,检测单核苷酸多态性(SNP),包括MPO rs7208693、MPO rs2243828和TIMP1 rs6609533。未观察到MPO基因多态性(rs7208693和rs2243828)与PE风险之间存在显著关联,而发现TIMP1 rs6609533 A>G SNP与PE易感性之间存在显著关联。具体而言,与携带AA基因型的个体相比,携带GG或AG基因型的个体患PE的风险更高。此外,在PE组中,携带G等位基因的患者更易发生胎儿生长受限(FGR)。在非PE组中,G等位基因与FGR风险之间的关联不明显。总之,中国汉族女性中TIMP1 rs6609533 G等位基因被确定为PE的一个危险因素。我们的结果表明,TIMP1 rs6609533 SNP可作为PE临床诊断和治疗的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a258/11403484/7474c2a36e5f/gr1.jpg

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