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.Kan N.E., Tyutyunnik N.V., Bednyagin L.A., Kharchenko D.K., Dolgushina N.V., Donnikov A.E., Tyutyunnik V.L.
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-onset preeclampsia (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-onset preeclampsia 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.
Keywords
preeclampsia
detoxication genes
genes` polymorphisms
risk factors
Supplementary Materials
- Table 1. Association between detoxication genes’ polymorphisms and preeclampsia
- Таble 2. Association between detoxication genes` deletions with preeclampsia
- Formula 1. Probability of early preeclampsia development depending on the revealed risk factors
References
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Received 14.06.2017
Accepted 23.06.2017
About the Authors
Kan Natalia E., PhD, MD, the head of the obstetric department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79262208655. E-mail: kan-med@mail.ru. Researcher ID B-2370-2015. ORCID ID 0000-0001-5087-5946
Tyutyunnik Nataliya V., the resident of the Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954380988. E-mail: tysia07@bk.ru
Bednyagin Lev A., student of the department of Fundamental Medicine of M.V. Lomonosov Moscow State University оf Moscow.
119991, Russia, Moscow, Leninskiye Hills 1. Tel.: +79265568641. E-mail: levbed@mail.ru
Kharchenko Daria K., the resident of the Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79151658700. E-mail: drkharchenko@mail.ru
Dolgushina Nataliya V., M.D., Ph.D., M.P.H., Head of R&D Department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954384977. E-mail: n_dolgushina@oparina4.ru
Donnikov Andrey E., M.D., Ph.D., the head of the molecular-genetic laboratory, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954384951. E-mail: a_donnikov@oparina4.ru
Tyutyunnik Victor L., PhD, MD, the head of the obstetric physiological department, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79039695041. E-mail: tioutiounnik@mail.ru. Researcher ID B-2364-2015.ORCID ID 0000-0002-5830-5099
For citations: Kan N.E., Tyutyunnik N.V., Bednyagin L.A., Kharchenko D.K., Dolgushina N.V., Donnikov A.E., Tyutyunnik V.L. Integrated approach to preeclampsia prediction based on molecular genetics and clinical factors. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (4): 35-41. (in Russian)
https://dx.doi.org/10.18565/aig.2018.4.35-41
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