CLINICAL PROFILE FEATURES, UTERINE ARTERY DOPPLER AND RENIN ANGIOTENSIN SYSTEM (RAS) POLYMORPHISMS IMPACT ON THE RISK FOR PREECLAMPSIA IN A ROMANIAN POPULATION

CLINICAL PROFILE FEATURES, UTERINE ARTERY DOPPLER AND RENIN ANGIOTENSIN SYSTEM (RAS) POLYMORPHISMS IMPACT ON THE RISK FOR PREECLAMPSIA IN A ROMANIAN POPULATION

Georgiana Nemeti*, Gabriela Caracostea*, Lucia Maria Procopciuc**, Mădălina Văleanu***, F. Stamatian*

* Department of Obstetrics and Gynecology I, „Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
** Department of Medical Biochemistry, „Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
*** Department of Medical Informatics & Biostatistics, „Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

 

Rezumat: Impactul profilului de risc clinic şi al polimorfismelor SRAA (sistemul renină-angiotensină-aldosteron) asupra riscului de preeclampsie la un lot de paciente din România

Preeclampsia este o complicaţie obstetricală ce are ca substrat etiopatogenic disfuncţia endotelială cu maladaptare vasculară consecutivă. Polimorfismele proteinelor SRAA au fost incriminate ca posibilă cauză a perfuziei utero-placentare deficiente. Scopul acestui studiu este acela de a stratifica riscul de preeclampsie la un lot de paciente din România pe criterii clinice şi ce aparin de genetica SRAA. În lotul caz au fost incluse 11 paciente cu hipertensiune indusă de sarcină, preeclampsie formă medie/severă, iar în lotul martor au fost incluse 100 de gravide normotensive. În casrul profilui de risc clinic au fost analizate vârsta maternă, paritatea, vârsta gestaţională, indicele de masă corporală pregestaţional, fumatul şi consumul de contraceptive. Polimorfismele SRAA studiate au fost determinate la toate cazurile: A235T angiotensinogen, T174M angiotensinogen, I/D şi ACE 8 în gena enzimei de conversie a angiotensinei, polimorfismul A1166C al receptorului 1 al angiotensinei II. La lotul caz, caracteristicle clinice confirmate a creşte frecvenţa preeclampsiei formă severă au fost nuliparitatea OR =5 (95%CI 2.1-28.9) şi obezitatea OR=3.1 (95%CI 0.89-26.5). Polimorfismele M235T angiotensinogen, ACE I/D şi AGTR-1 A1166C au fost asociate cu preeclampsia formă severă (OR=2.6 (95%CI 1.1 – 18.1), OR=1,8 (95%CI 1 – 15,2), respectiv OR=2,3 (95%CI 1,4 – 12,4)). Studiul de faă demostrează că nuliparitatea şi obezitatea ca parametri clinici, precum şi alelele mutante M235T angiotensinogen, ACE I/D şi A1166C AGTR-1 ca parametri genetici se asociază cu preeclampsia cu prognostic sever.

      

Abstract

       Preeclampsia is a pregnancy associated complication characterized by endothelial dysfunction and consequent vascular maladaptation. Genetic variants of RAS proteins have been proposed as possible cause of the deficient uteroplacental perfusion. This study aimed at risk stratification according to clinical and genetic features related to RAS polymorphysms in a group of preeclamptic Romanian patients. 111 patients were enrolled in the study group, diagnosed with pregnancy induced hypertension, mild and severe preeclampsia and 100 patients with normotensive pregnancies in the control group. The clinical profile parameters analyzed were maternal age, parity, gestational age, pregestational body mass index (BMI), smoking habit and contraceptive use. Genetic evaluation of RAS polymorphisms including A235T angiotensinogen, T174M angiotensinogen, angiotensin converting enzyme (ACE) I/D, ACE 8 and thr A1166C variant of type 1 receptor for angiotensin IIAGTR1 were performed in all cases. The clinical profile of the study group patients confirmed the increased frequency of severe disease in nulliparous OR =5 (95%CI 2.1-28.9) and obese OR=3.1 (95%CI 0.89-26.5) patients. The M235T angiotensinogen, ACE I/D and A1166C AGTR-1 genetic variants associated an increased frequency of the severe form of the disease (OR=2.6 (95%CI 1.1 – 18.1), OR=1,8 (95%CI 1 – 15,2), respectively OR=2,3 (95%CI 1,4 – 12,4)). The present study shows that nulliparity and increased pregestational BMI as clinical parameters and M235T angiotensinogen, ACE I/D and A1166C AGTR-1 allele as genetic parameters are associated with a severe outcome in preeclampsia.

Keywords: preeclampsia, predicţie, SRAA, risc clinic