AQUAPORIN-3 AND HEPARANASE GENETIC POLYMORPHISMS MAY MODULATE ANGIOGENESIS INFLUENCING THE RISK OF HYPERTENSIVE DISORDERS IN WOMEN

Abstract

Objective: Preeclampsia (PE), a pregnancy complication triggered by oxidative stress and hypoxia, compromises mother and baby health and changes mother’s blood vessels increasing the risk for hypertension(HT). Aquaporin-3 (AQP3) is a water/H2O2/glycerol channel with implications in redox signaling. Heparanase (HPSE) has a role in extracellular matrix remodeling during angiogenesis. So far, no relation between AQP3 and HPSE genetic polymorphisms in PE subjects has been addressed. Thus, we aimed to investigate the association of AQP3(rs2231231) and HPSE(rs4693608) polymorphisms with the development of hypertensive disorders in women. Design and method: We investigated the distribution of AQP3 and HPSE genetic variations in a cohort of 150 normotensive (NT) or PE women, along with intermediate phenotype and anthropometric parameters. In a prospective study, women were reclassified 2–16 years after being PE or NT during pregnancy as NT or HT and genetic associations were reevaluated. Data was analyzed using SPSS software, P-values < 0.05 were statistically significant. Results: No differences were found in the distribution of the studied polymorphisms in PE. Allele A of AQP3 was more prevalent in HT after pregnancy(P = 0.014) and correlated with subjects with increased systolic(P = 0.017) and diastolic(P = 0.008) blood pressures. Moreover, allele A was considered the allele of risk, associated with a 3.53-fold higher risk(P = 0.018) to develop HT after pregnancy. In this cohort, serum myeloperoxidase (MPO) higher levels correlated with PE (P = 0.000) and HT (P = 0.024) and were associated with HT after a NT pregnancy(P = 0.000). Although HPSE did not correlate with PE or HT, Allele A carriers were associated with increased Apolipoprotein A(ApoA;P = 0.027), uric acid(P = 0.027) and MPO(P = 0.005) in PE. In HPSE, PE subjects with allele G correlated with increased number of leucocytes(P = 0.048) while the presence of allele A was associated with decreased serum uric acid(P = 0.028). When the 4 groups were reevaluated, allele A of HPSE was associated with decreased blood glucose levels(P = 0.05) and increased pulse pressure(P = 0.003) and uric acid(P = 0.05) in women that had PE. Allele G was more frequent with lower levels of leucocytes(P = 0.024) in women that had PE and later HT. Conclusions: The AQP3 polymorphism is a promising biomarker for HT. HPSE polymorphism predicts PE-associated variations in the intermediate phenotype.