Molecular Genetic Determinants of Impaired Lipid Metabolism in the Pathogenesis of Preeclampsia
https://doi.org/10.31550/1727-2378-2024-23-8-32-40
Abstract
Aim. To study the role of lipid metabolism gene polymorphism and changes in the lipid-transporting lipid system in patients with moderate to severe preeclampsia (PE).
Design. Prospective cohort comparative study.
Materials and methods. We analysed results of clinical, anamnestic and laboratory examination of 130 patients with a high risk of PE, following a prenatal diagnostics performed during the first trimester. The patients were divided into three groups: with actual severe PE (group I, n = 53, weeks 23 to 38 of pregnancy); with actual moderate PE (group II, n = 45, weeks 28 to 40 of pregnancy), and without PE (control group, or group III, n = 32, weeks 28 to 40 of pregnancy).
During the clinical examination, somatic and obstetric-gynaecological history was taken, and the present pregnancy was reviewed. A sample for blood biochemistry was drawn upon hospitalisation; the analysis included lipid parameters (cholesterol, triglycerides, high, low and very low-density lipoproteins), total bilirubin, urea, creatinine, apolipoproteins (АроА, АроВ). Sample genotyping was performed using the realtime polymerase chain reaction with a reagent kit and protocol for genetic polymorphisms.
Results. The results show that the most informative parameters of dyslipidaemia in pregnant women, which are associated with the risk of PE, are high levels of very low-density lipoproteins, atherogenic index of over 3.5 and ApoB/ApoA index of over 0.9.
The presence of allele T of polymorphic locus ApoE rs429358 in homo- or heterozygous state in the genotype increases the risk of PE, while genotype СС of polymorphism ApoE rs429358 has a protective effect against this pathology. Genotype AA of polymorphism rs708272 of gene CETP (G>A) has also a protective effect, while the presence in the genotype of at least one variant of allele G of this locus increases the risk of PE.
Conclusion. The study demonstrates the importance of lipid transport system parameters, especially the ratio of apolipoproteins and various density lipoproteins, as well as polymorphisms ApoE T>C, CETP G>A in the pathogenesis and diagnosis of PE.
About the Authors
N. V. BashmakovaRussian Federation
Ekaterinburg
A. A. Denisov
Russian Federation
Ekaterinburg
T. B. Tretyakova
Russian Federation
Ekaterinburg
L. A. Pestryaeva
Russian Federation
Ekaterinburg
A. Yu. Semenov
Russian Federation
Moscow
References
1. Chaudhary S., Hiranwal M., Chaudhary D., Dudi P. Hyperlipidemia of pregnancy: normal or predictor of preeclampsia. J. South Asian Fed. Obstet. Gynaecol. 2020;12(1):31–3. DOI: 10.5005/jp-journals-10006-1752
2. Sadullaeva O.R., Mamieva L.M. Lipid profile indicators in pregnant women depending on gestation period. Journal of Theoretical and Clinical Medicine. 2021;6:136–8. (in Russian).
3. Kapustin R.V., Tsybuk E.M., Alexeyenkova E.N., Kopteyeva E.V. et al. The role of dyslipidemia in the pathogenesis of perinatal complications in pregnant women with diabetes mellitus. Journal of Obstetrics and Women’s Diseases. 2021;70(1):89–100. (in Russian). DOI: 10.17816/JOWD48566
4. Wild R., Feingold K.R. Effect of pregnancy on lipid metabolism and lipoprotein levels. Last update: March 3, 2023. URL: https:// www.ncbi.nlm.nih.gov/books/NBK498654/ (дата обращения — 25.10.2024).
5. El Khouly N.I., Sanad Z.F., Saleh S.A., Shabana A.A. et al. Value of first-trimester serum lipid profile in early prediction of preeclampsia and its severity: a prospective cohort study. Hypertens. Pregnancy. 2016;35(1):73–81. DOI: 10.3109/10641955.2015.1115060
6. Catov J.M., Bodnar L.M., Kip K.E.. Hubel C. et al. Early pregnancy lipid concentrations and spontaneous preterm birth. Am. J. Obstet. Gynecol. 2007;197(6):610.e1–7. DOI: 10.1016/j.ajog.2007.04.024
7. Jin W.Y., Lin S.L., Hou R.L., Chen X.Y. et al. Associations between maternal lipid profile and pregnancy complications and perinatal outcomes: a population-based study from China. BMC Pregnancy Childbirth. 2016;16(1):60. DOI: 10.1186/s12884-016-0852-9
8. Wang X., Guan Q., Zhao J., Yang F. et al. Association of maternal serum lipids at late gestation with the risk of neonatal macrosomia in women without diabetes mellitus. Lipids Health Dis. 2018;17(1):78. DOI: 10.1186/s12944-018-0707-7
9. Misra V.K., Trudeau S., Perni U. Maternal serum lipids during pregnancy and infant birth weight: the influence of prepregnancy BMI. Obesity (Silver Spring). 2011;19(7):1476–81. DOI: 10.1038/oby.2011.43
10. Mudd L.M., Holzman C.B., Evans R.W. Maternal mid-pregnancy lipids and birthweight. Acta Obstet. Gynecol. Scand. 2015;94(8):852–860. DOI: 10.1111/aogs.12665
11. Bendix E.J., Ravn J.D., Sperling L., Overgaard M. First trimester serum apolipoproteins in the prediction of late-onset preeclampsia. Scand. J. Clin. Lab. Invest. 2023;83(1):23–30. Epub. 2022 Dec. 20. DOI: 10.1080/00365513.2022.2155991
12. Stadler J.T., Scharnagl H., Wadsack C., Marsche G. Preeclampsia affects lipid metabolism and HDL function in mothers and their offspring. Antioxidants (Basel). 2023;12(4):795. DOI: 10.3390/antiox12040795
13. Ramanjaneya M., Butler A.E., Bashir M., Bettahi I. et al. ApoA2 correlates to gestational age with decreased apolipoproteins A2, C1, C3 and E in gestational diabetes. BMJ Open Diabetes Res. Care. 2021;9(1):e001925. DOI: 10.1136/bmjdrc-2020-001925
14. Liu Z., Pei J., Zhang X., Wang C. et al. ApoA1 is a novel marker for preeclampsia. Int. J. Mol. Sci. 2023;24(22):16363. DOI: 10.3390/ijms242216363
15. Shekhireva T.V. Modern markers of early subclinical atherosclerosis detecting risk factors of cardiovascular diseases. Academic Journalism. 2021;8–1:97–114. (in Russian).
16. Raina J.K., Sharma M., Panjaliya R.K., Dogra V. et al. Association of ESR1 (rs2234693 and rs9340799), CETP (rs708272), MTHFR (rs1801133 and rs2274976) and MS (rs185087) polymorphisms with Coronary Artery Disease (CAD). BMC Cardiovasc. Disord. 2020;20(1):340. DOI: 10.1186/s12872-020-01618-7
17. Gabidullina R.I., Ganeeva A.V., Shigabutdinova T.N. Predictors of preeclampsia. Screening and prophylaxis in the I trimester of pregnancy. Gynecology. 2021;23(5):428–34. (in Russian). DOI: 10.26442/20795696.2021.5.201213
18. Tan M.Y., Syngelaki A., Poon L.C., Rolnik D.L. et al. Screening for pre-eclampsia by maternal factors and biomarkers at 11–13 weeks' gestation. Ultrasound Obstet. Gynecol. 2018;52(2):186–95. DOI: 10.1002/uog.19112
19. Bartsch E., Medcalf K.E., Park A.L., Ray J.G.; High Risk of Preeclampsia Identification Group. Clinical risk factors for preeclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies. BMJ. 2016;353:i1753. DOI: 10.1136/bmj.i1753
20. Rong K., Yu K., Han X., Szeto I.M. et al. Pre-pregnancy BMI, gestational weight gain and postpartum weight retention: a meta-analysis of observational studies. Public Health Nutr. 2015;18(12):2172–82. Epub. 2014 Nov. 20. DOI: 10.1017/S1368980014002523
21. Vekic J., Zeljkovic A., Stefanovic A., Jelic-Ivanovic Z. et al. Obesity and dyslipidemia. Metabolism. 2019;92:71–81. Epub. 2018 Nov. 14. DOI: 10.1016/j.metabol.2018.11.005
22. Timur H., Daglar H.K., Kara O., Kirbas A. et al. A study of serum Apo A-1 and Apo B-100 levels in women with preeclampsia. Pregnancy Hypertens. 2016;6(2):121–5. DOI: 10.1016/j.preghy.2016.04.003
23. Nurieva L.M., Kim Z.F., Galyavich A.S., Sadykova D.I. Hypertriglyceridemia and atherosclerotic cardiovascular diseases. The Bulletin of Contemporary Clinical Medicine. 2023;16(4):104–10. (in Russian). DOI: 10.20969/VSKM.2023.16(4).104-110
24. Kononov S.I., Mal G.S., Churilin M.I., Azarova Yu.E. et al. Polymorphic rs7412 in APOE gene as a predictor of ischemic heart disease risk and effectiveness of Rosuvastatin therapy. Kursk Scientific and Practical Bulletin "Man and His Health". 2019;1:5–13. (in Russian). DOI: 10.21626/vestnik/2019-1/01
Review
For citations:
Bashmakova N.V., Denisov A.A., Tretyakova T.B., Pestryaeva L.A., Semenov A.Yu. Molecular Genetic Determinants of Impaired Lipid Metabolism in the Pathogenesis of Preeclampsia. Title. 2024;23(8):32-40. (In Russ.) https://doi.org/10.31550/1727-2378-2024-23-8-32-40