Integrated approach to preeclampsia prediction based on molecular genetics and clinical factors

Objective. To study the significance of detoxication genes’ polymorphisms in preeclampsia development and to create preeclampsia prediction model. Materials and methods. 241 patients who were delivered in Federal State Budget Institution “Research Center for Obstetrics, Gynecology and Perinatology” Ministry of Healthcare of the Russian were involved in the study. All patients were divided into 3 groups: 1А group (43 women) - patients with early-onset preeclampsia (developed before 34 weeks of gestation), 1B group (49 women) - patients with late-onsetpreeclampsia (developed after 34 weeks of gestation), 2 - control group (149 women). We conducted a cross-sectional study in parallel groups: genetic analysis in patients with preeclampsia and patients with normal pregnancy. Genotyping PCR method was performed with melting curve analysis, modified method of «adjacent probes» («kissing probes») by means of commercial test system «Scientific-Production Association (NPO) DNA-Technology ООО» (Limited Liability Company), Russia. Multifactorial analysis was performed for early-onset and late-onsetpreeclampsia individual risk assessment based on genetic, clinical and anamnestic risk factors. Results. We developed an individual risk assessment formula of early-onset and late-onset preeclampsia development based on multifactorial analysis' data, clinical and anamnestic risk factors. Age of patients, BMI, CYP1A1 (rs4646903) polymorphism, a history of preeclampsia and pelvic inflammatory diseases have a great impact on probability of early-onset preeclampsia development. We found that detoxication genes’ polymorphisms could be referred to potential pathogenetic factors of preeclampsia development. Detoxication genes’ polymorphisms (CYP1A1 и GSTP1) are more typical for pregnancy complicated by preeclampsia in comparison to normal pregnancy. This fact proves that detoxication genes’ polymorphisms (CYP1A1 и GSTP1) could be used as preeclampsia development predictors. Conclusion. We investigated 16 single nucleotide detoxication genes' polymorphisms in healthy pregnant women and in patients with early-onset and late-onset preeclampsia. We found significant association of several genes with early-onset and late-onset preeclampsia development. Some of these genes proved to be significant in multifactorial analysis and were used in the creation of a model of individual risk assessment of preeclampsia development.

preeclampsia, detoxication genes, genes' polymorphisms, risk factors