AQUAPORIN-3 AND CYBA GENETIC POLYMORPHISMS MAY PREDICT RISK OF DEVELOPING HYPERTENSION

Abstract

Objective: Preeclampsia, a placentation disorder, affects 7% of pregnancies in Europe. It influences future cardiovascular disease, such as hypertension. Preeclampsia and hypertension have been associated with oxidative stress, therefore, key proteins in redox signaling may be involved with the development of hypertensive disorders during/after pregnancy. This study aimed at determining associations between oxidative stress-related gene polymorphisms (AQP3-rs2231231 and CYBA-rs4673) with the development of preeclampsia and the risk for future hypertension. Design and method: A cohort of 150pregnant Caucasian women, aged 35.24 ± 5.47 years, 60(40%) normotensive and 90(60%) preeclamptic, was evaluated. Based on a prospective study(2–16 years later), these women were evaluated for the development of hypertension and classified as normotensive 98(67%) or hypertensive 48(33%). The influence of genetic polymorphisms on the susceptibility for cardiovascular disease was evaluated. In this cohort, anthropometric/haemodynamic parameters were studied. For statistical analysis chi-square and Student t-test were used. Results: During pregnancy, no differences between the distribution of studied genetic polymorphisms in preeclampsia were found. However, based on the AQP3 dominant model of A, our data showed that AA+AC genotypes were more frequent (73.3%;p = 0.014) in hypertensive individuals. Moreover, allele A, the allele of risk, was associated with a 3.405-fold higher risk (p = 0.016,OR = 3.405,95%CI[1.26–9.19]) to develop hypertension after pregnancy. In addition, a higher systolic(p = 0.017) and diastolic(p = 0.008) pressure were also observed in women carrying the AA+AC genotype. Furthermore, based on CYBA dominant model of C, TT genotype of polymorphism was also correlated with the development of hypertension(100.0%;p = 0.007) after pregnancy. On the other hand, looking at the recessive model of C, CT+TT genotype was associated with the development of hypertension. Allele T, the allele of risk, was associated with 6.5-fold risk (p = 0,024,OR = 6.500,95%CI[1.28–33.03] to develop hypertension. Moreover, CT+TT genotypes of CYBA genetic polymorphism were more associated with increased weight (p = 0.014), higher waist circumference(p = 0.010), hip(p = 0.008) and systolic(p < 0.001) and diastolic blood pressure(p < 0.001). Conclusions: In this study, AQP3 genetic polymorphism was found associated with the hypertensive disorders after pregnancy for the first time. In addition, CYBA was also associated with the development of essential hypertension. These results open new perspectives in the development of new approaches for cardiovascular disease prevention.