Association of Aquaporin-3, Aquaporin-7, NOS3 and CYBA polymorphisms with hypertensive disorders in women

Abstract

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.

Keywords: Aquaporins; Hypertension; Metabolic Syndrome; Oxidative Stress; Polymorphisms; Preeclampsia.