Genetic markers for prediction of early and late onset preeclampsia in pregnant women with preexisting type 1 diabetes mellitus




pregnancy, type 1 diabetes mellitus, early- and late-onset preeclampsia, prediction, genetic markers, gene polymorphism, gene-gene interactions


The study compared the profile of polymorphic variants of genes that determine the basic pathogenesis of pre-eclampsia in groups of patients with type 1 diabetes. Overall, 60 female patients with type 1 diabetes were investigated: pregnancy complicated with early-onset (n = 15) and late-onset (n = 15) superimposed preeclampsia was reported in 30 subjects; no complications were detected among the rest 30 patients. Besides standard clinical investigation, each patient underwent molecular genetic testing with detection of the following polymorphic variants of genes: А1166С-AT2R1, C108T-PON1, Thr83Ala- and T138C-MGP, 4b/4a- and G894T-eNOS, as well as I/D-ACE.

On completion of our study we established differential prognostic models for prediction of early-and late-onset preeclampsia development in women with pre-existing type 1 diabetes mellitus based on the data about the prevalence of polymorphic variants of genes and gene-gene interactions.

The following risk factors were found to be the main contributors to early-onset (< 32 weeks) preeclampsia development: long duration of diabetes; presence of vascular complications at the time of conception (in particular, diabetic angiopathy of lower extremities and diabetic nephropathy); and ACE ID-genotype. The most significant genotype combinations associated with early-onset preeclampsia development were as follows: ACE (ID) / AT2R1 (1166АА), ACE (ID) / AT2R1 (1166АС), ACE (I/D) / eNOS (4b/4b), ACE (I/D) / eNOS (894GG). Genetic factor influenced the development of late-onset preeclampsia (≥ 32 weeks) to a much lesser extent; only one statistically significant combination of genotypes was detected to be associated with preeclampsia debut after 32 weeks of pregnancy – ACE (ID) / MGP (138TC). Genotype combination ACE (II) / PON1 (108CC) significantly reduced the risk of preeclampsia development during the entire pregnancy.

Important genetic markers found in our study will allow predicting different forms of preeclampsia in type 1 diabetic pregnant women. Identification of women at high risk for early-onset preeclampsia development will let us to implement treatment and preventive measures and to provide closer monitoring, resulting in better pregnancy outcomes.

Author Biographies

Т. В. Авраменко, Institute of Pediatrics, Obstetrics and Gynecology NAMS of Ukraine

MD, professor, head of the Department of Obstetrics Endocrinology and Fetal Defects

А. В. Грибанов, Institute of Pediatrics, Obstetrics and Gynecology NAMS of Ukraine; Nikolaev City Maternity Hospital № 2

Clinical research fellow at the Department of Obstetrics Endocrinology and Fetal Defects; obstetrician gynecologist 

З. И. Россоха, Reference Center for the Molecular Diagnosis of the Ministry of Health of Ukraine

PhD, director 


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How to Cite

Авраменко, Т. В., Грибанов, А. В., & Россоха, З. И. (2015). Genetic markers for prediction of early and late onset preeclampsia in pregnant women with preexisting type 1 diabetes mellitus. REPRODUCTIVE ENDOCRINOLOGY, (26), 56–65.



Pregnancy and childbirth