Marcadores moleculares associados à pré-eclâmpsia

Abstract

Preeclampsia, or pregnancy-specific hypertensive disease, is a pathology which, despite obstetrical care, occurs during pregnancy causing discomfort for both mother and fetus. Preeclampsia is a syndrome unique to pregnancy. Hypertension, edema and proteinuria are some of the characteristics of its manifestation. Even though many advancements have been done in the last years, studíes still couldn’t establish an etiology for the disease. It’s believed to be a multiple-cause disease and genetic factors are believed to be involved on it’s manifestation. During a normal pregnancy several physiological modifications occur. RAAS, which is responsible for muscular tonus, hydric balance and salt homeostasis maintenance, suffers changes that, in a preeclampsia pregnancy, become harmful to the pregnant woman’s health. Another extensively affected System is the blood clotting system, which is said to be in hypercoagulable State. The present study analyses the angiotensinogen variant M235T, the angiotensin I converting enzyme l/D polymorphism, the angiotensin II receptor I variant A1166C, which are RAAS components, and genetic variants of Factor V of Leiden, R06Q, and protrombin A20210G, which are part of the blood coagulation chain. Peripheral blood samples for DNA exctraction and genotyping were collected under a term of agreement from 50 preeclamptic pregnant women and 47 normal pregnant women. Genotipícal and allelic frequencies for each gene were calculated and no statistically significant differences were found between the studied groups. Angiotensinogen was the only gene to show statistically significant canonical correlation with preeclampsia manifestation (R= 0.21 p<0.035) and there was a small increase on this correlation when the Factor V of Leiden gene was included in the analysis (R= 0.26 p<0.035). The estimated effect on the odds ratio for the angiotensinogen gene was 2.16, i.e., heterozigous M235T women have 2.16 times greater risk to develop preeclampsia than M/M , and T/T genotype predisposes women to 4.32 times greater risk to develop preeclampsia when compared to M/M homozygotes. The analysis of non-genetic risk factors (age, number of pregnancies, presence of edema, systemic systolic and diastolic blood37 pressure) related to occurrence of preeclampsia was statistically significant (R= 0.83 p<0.00001). Therefore, non-genetic factors influenced preeclampsia manifestation in about 80% of the cases studied, and among genetic factors, angiotensinogen was the only one that contributed in 20% of cases. Even though the results of this study have suggested a stronger influence by non-genetic factors, genetic evaluation of subjects with a family predisposition for preeclampsia, or suspect clinicai situation is very important for early diagnosis and disease prevention, avoiding morbidity and mortality for both pregnant woman and fetus.