Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal; Departamento de Ciências Farmacêuticas e do Medicamento, Faculdade de Farmácia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003 Lisboa, Portugal.
Laboratório de Genética, Instituto de Saúde Ambiental, Faculdade de Medicina, Universidade de Lisboa, 1649-026 Lisboa, Portugal; Instituto de Investigação Científico Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal.
Pregnancy Hypertens. 2021 Jun;24:44-49. doi: 10.1016/j.preghy.2021.02.008. Epub 2021 Feb 23.
Preeclampsia (PE), a pregnancy disorder influenced by oxidative stress and hypoxia, affects the health of the mother and baby and is associated with an increased risk of future hypertension (HT). Aquaporins are a family of water channels, comprising members that also transport glycerol (aquaglyceroporins) and hydrogen peroxide (peroxiporins), key molecules for metabolic homeostasis and redox signaling. Here, we investigated the association of Aquaporin-3 (AQP3; rs2231231), Aquaporin-7 (AQP7; rs2989924), NOS3 (4B/A intron) and CYBA (rs4673) genetic polymorphisms with the development of hypertensive disorders by qPCR/PCR in a cohort of 150 normotensive (NT) women (N = 90) or with previous PE (N = 60) during pregnancy. Prospectively, women were reclassified 2-16 years after pregnancy as NT (N = 98) or hypertensive (N = 48) and the genetic associations were reevaluated. In addition, genetic associations were reevaluated and compared between normotensive and hypertensive (HT) subjects. We found that AQP3 rs2231231, an aquaglyceroporin/peroxiporin, is associated with the development of HT, whereas AQP7, NOS3 and CYBA polymorphism did not correlate with PE or future HT. Because AQP3 was associated with hypertension only after pregnancy, its role might be related to later risk factors of hypertension such as metabolic syndrome or oxidative stress.
子痫前期 (PE) 是一种受氧化应激和缺氧影响的妊娠疾病,会影响母婴健康,并增加未来发生高血压 (HT) 的风险。水通道蛋白是一类水通道,包括也运输甘油 (aquaglyceroporins) 和过氧化氢 (peroxiporins) 的成员,这些是代谢稳态和氧化还原信号的关键分子。在这里,我们通过 qPCR/PCR 在 150 名正常血压 (NT) 女性 (N=90) 或有既往子痫前期 (PE) 病史的孕妇 (N=60) 队列中研究了 Aquaporin-3 (AQP3; rs2231231)、Aquaporin-7 (AQP7; rs2989924)、NOS3 (4B/A 内含子) 和 CYBA (rs4673) 遗传多态性与高血压疾病发展的相关性。前瞻性地,在产后 2-16 年后,将这些女性重新分类为 NT (N=98) 或高血压 (HT) (N=48),并重新评估遗传相关性。此外,我们还重新评估了在 NT 和 HT 受试者之间的遗传相关性。我们发现,作为 aquaglyceroporin/peroxiporin 的 AQP3 rs2231231 与 HT 的发生有关,而 AQP7、NOS3 和 CYBA 多态性与 PE 或未来 HT 无关。由于 AQP3 仅在产后与高血压相关,其作用可能与代谢综合征或氧化应激等高血压的后期危险因素有关。