Analysis of the Influence of Polymorphisms of Maternal CYP1B1 Gene in Gestational Age of Birth: a Clinical and Molecular Correlation
Name: JÉSSICA AFLÁVIO DOS SANTOS
Publication date: 20/04/2017
Advisor:
Name |
Role |
|---|---|
| IURI DRUMOND LOURO (M/D) | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| IURI DRUMOND LOURO (M/D) | Advisor * |
| MARCELO DOS SANTOS | External Examiner * |
Summary: Currently, both prematurity and births occurring in the late preterm and in the early term have been highlighted by their negative influence on infant mortality and morbidity. Several risk factors have been associated with decreased gestational age at birth. Environmental risk factors include cigarette smoking, excessive alcohol intake, ethnicity, weight and maternal age. Regarding genetic factors, genetic polymorphisms involved in oxidative stress and xenobiotics metabolism have been strongly associated with preterm birth. This may generate oxidative stress, considered a primary etiological factor for preterm birth because it can cause a compromised placenta. This is the case of the CYP1B1 gene, which also plays an important role in the estrogen synthesis, one of the most important hormones in pregnancy maintenance. The action of the enzyme CYP1B1 may result in the production of reactive and carcinogenic compounds due to the preferential hydroxylation of 17β-estradiol at the 4-hydroxy position. The polymorphisms rs10012, rs1056827, rs1056836 were selected for this work because they are associated with variations in this enzyme activity. Thus, the present study aims to investigate the possible influence of these polymorphisms, as well as clinical data and maternal life habits in gestational age at birth. For such, a prospective cohort study was carried out with pregnant women from the Santo Antônio de Jesus city, in State of Bahia, Brazil. Mothers were followed during gestation, delivery and puerperium between 2009 and 2016. Maternal characteristics and habits were obtained through standardized questionnaires. Genotyping was performed from blood samples from pregnant women with TaqMan® assays using the Real Time Polymerase Chain Reaction (PCR) technique. Pregnant women who delivered in the initial full-term period had higher mean maternal age and pre-gestational Body Mass Index (BMI) than the preterm and full-term periods. Pre-gestational BMI intervals, race, smoking, and alcoholic showed no significant association with gestational age at birth. A significant correlation was detected between the SNP rs1056836 and the maternal age and the pre-gestational BMI. None of the other analyzed variables showed a significant association with any of the other polymorphisms. Non direct association was detected between any of the analyzed polymorphisms and gestational age at birth. From the results obtained by this work, a possible relationship of the CYP1B1 gene with the gestational age at birth can not be ruled out. Subsequent studies should analyze the possible association of these polymorphisms with gestational age at birth in other ethnic groups, as well as carry out
more extensive investigations including other genes and polymorphisms, as well as prematurity environmental risk factors.
