CYP17A1 gene polymorphisms and environmental exposure to organochlorine pesticides contribute to the risk of small for gestational age

Abstract

ObjectivesThe cytochrome P-450c17α enzyme encoded by the cytochrome P-450c17α (CYP17A1) gene plays a role in oestrogen synthesis. Genetic variation in the maternal CYP17A1 gene leads to differences in oestrogen level that affect fetal growth and cause small for gestational age (SGA). Organochlorine pesticides (OCPs) are endocrine disruptors that alter the normal oestrogen–progesterone balance, and are associated with adverse reproductive outcomes. This study was designed to investigate the effect of the gene–environment interaction between maternal CYP17A1 gene polymorphisms and maternal and cord OCP levels on the risk of SGA. Study designMaternal and cord blood samples of 50 term SGA cases (birth weight <10th percentile for gestational age as per Lubchenco's growth chart) and 50 normal pregnancies (controls) were collected. Women with occupational exposure to OCPs, anaemia, hypertension, antiphospholipid antibody syndrome, medical disease, parity of more than four, or a history of smoking, alcohol consumption or chronic drug intake were excluded from both groups. Maternal and cord blood samples were collected at the time of delivery or after delivery, respectively. The OCP levels of the samples were analyzed using a gas chromatography system equipped with an electron capture detector, and polymerase chain reaction–restriction fragment length polymorphism was used for polymorphic analysis of the CYP17A1 gene. ResultsSignificantly (p<0.05) higher levels of α-hexachlorocyclohexane (HCH), β-HCH and γ-HCH were found in maternal and cord blood samples of the SGA cases compared with the controls. The frequency of the A1A2/A2A2 genotype was significantly lower [p=0.041, odds ratio (OR) 0.421, 95% confidence interval (CI) 0.184–0.966] in the SGA cases compared with the controls. When gene–environment interactions between CYP17A1 gene polymorphisms and OCP levels were considered, a significant (p=0.004) association was found between a high level of endosulfan in cord blood and the A1A1 (wild-type) genotype of CYP17A1, leading to an estimated reduction in birth weight of 315g. ConclusionsHigher OCP levels and the A1A1 genotype of CYP17A1 in pregnant women may be considered as important aetiological factors in idiopathic SGA. This study provides evidence that genetic variation and its interaction with environmental exposure may increase the risk of SGA. Further studies are needed with a larger sample size, incorporating other gene polymorphisms and environmental exposures, to strengthen these observations.