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