This study, which aimed to investigate the polymorphisms of VEGF gene in pregnant women with PE, showed that despite a significant increase of serum VEGF concentrations in these women, it appears that -634C/G and +936C/T polymorphisms of VEGF gene are not associated with the onset of PE.
Screening for PE using maternal factors and genomic variations is preferred to other tools such as taking a medical history (14). In this study, maternal age and BMI, pregnancy week, infant weight, and hemoglobin concentration were risk factors for PE. In this study, as in another research, the mean age of the case group was significantly different from the control group, indicating that the risk of PE increases with age (15). In another research, the average age of >35 was associated with PE (16). A study found that the lower the gestational age at delivery in the previous pregnancy, the higher the risk of PE in the next pregnancy, which was a strong determinant of the disease (17). While in another study, no association was found between age and PE (18). Besides, a study of adverse pregnancy outcomes using a national multicenter perinatal database reported that advanced maternal age (≥45) is related with greater risk of adverse birth outcomes, especially for maternal complications such as PE (19). Since the association of PE with >35 age has been proven in numerous studies (16), our research indicates that the PE risk may increase with age. Similar to our results, Jean-Ju Sheen and colleagues showed that older women were more likely to develop PE (20) .Therefore, since only women aged 18-37 years were included in this study, it can be said that the risk of PE increases with age in any age range of the mother. In this research, it was observed that increasing BMI increases the risk of PE, which is consistent with some other studies (21, 22). In a two-year cohort of the impact of maternal pre-pregnancy BMI and gestational weight gain on the risk of PE, the association between overweight and disproportionate weight gain with a higher risk of PE was shown (23). Another study identified overweight pregnant women and obesity as a risk factor for PE (24). Recently, another investigation assessed the effect of maternal weight on maternal and perinatal outcomes, suggesting that gestational weight gain affects the maternal and perinatal outcomes and that pre-gestational BMI is an indicator of PE (25). Moreover, another study found that hemoglobin levels in control and PE groups were not significantly different (26). A research found that the PE occurrence was more frequent in the summer (27); however, in the present study, there was no significant correlation between the occurrence season and PE. Recently, however, a study showed that elevated average temperature is a risk factor for pregnant women with PE, and this increase in temperature is more common in summer (28).
The hypothesis is that the imbalance of pro-angiogenic and anti-angiogenic factors in mother's bloodstream is a main regulator in the growth of normal endothelial function as one of the important characteristics of the disease. Early findings from a study showed that high levels of sFlt-1 expression by an adenovirus vector in rats can lead to gestational hypertension and renal proteinuria (27).
Recent studies on human genetics have revealed that genetic factors play a role in PE, but the exact genetic pattern is not clear. In this research, we tried to prove the relationship between VEGF gene and PE incidence. The role of VEGF in PE needs further attention. Several studies have reported the increase in serum levels of VEGF in women with PE (29, 30). Our study concluded that VEGF level increases in women with PE relative to the normal group, while a study concluded that the VEGF level is reduced in women with PE; this contradiction can be due to genetic variations in the studied populations or differences in the study population (31).
A study showed that in women with PE, an antagonist of VEGF known as Sflt-1 is increased in the blood of mothers with PE and the resulting rise in sflt-1 lowers serum VEGF levels, while the level of this VEGF antagonist was not changed in healthy pregnant women (31). In one study, it was found that the Sflt-1/ placental growth factor (PlGF) ratio is a valuable test in predicting adverse maternofetal outcomes (AMFO) in proven early-onset PE, which can improve the treatment process by predicting adverse effects(32). Considering the fact that most studies have been conducted on VEGF gene sequence in mothers, studying the level of VEGF in umbilical cord of infants as well as polymorphism of this gene in neonates is suggested.
The results of one study showed that there is an association between frequency of +936T allele and increased susceptibility to PE (33). But in our study, there was no significant correlation between the incidence of PE and this SNP, one of the most important reasons for which could be related to genetic differences. Since we did not investigate a single ethnic group in this research and our study population was a combination of different races, it is suggested that a study of the Iranian ethnic groups, including Lur, Kurd, Turk, and Arab, and so on to understand the role of race in this subject.
In our research, there was no significant correlation between PE incidence and -634G/C and +936C/T polymorphisms. Similar results were obtained in a study in which three SNPs of VEGF gene, including -2578C/A, -634G/C, and +366C/T were investigated using RFLP-PCR method. The obtained results showed that there is no relationship between these three SNPs and PE (12). Of course, one of the limitations of these two studies was the use of RFLP-PCR technique. Therefore, it is suggested that Real-time PCR method should be used to better investigate SNPs.
In another study, no significant relationship was seen between the allele frequency of three VEGF gene SNPs, including -460C/T, +405C/CG, and +936C/T with the incidence of endometriosis (34). In contrast to the present study, it was observed that VEGF level increased in sera of patients with PE, however, there was no significant relationship between the incidence of PE and +936C/T polymorphism.