Abstract
BackgroundPre-eclampsia is the most common complication occurring during pregnancy. In the majority of cases, it is concurrent with other pathologies in a comorbid manner (frequent co-occurrences in patients), such as diabetes mellitus, gestational diabetes and obesity. Providing bronchial asthma, pulmonary tuberculosis, certain neurodegenerative diseases and cancers as examples, we have shown previously that pairs of inversely comorbid pathologies (rare co-occurrences in patients) are more closely related to each other at the molecular genetic level compared with randomly generated pairs of diseases. Data in the literature concerning the causes of pre-eclampsia are abundant. However, the key mechanisms triggering this disease that are initiated by other pathological processes are thus far unknown. The aim of this work was to analyse the characteristic features of genetic networks that describe interactions between comorbid diseases, using pre-eclampsia as a case in point.ResultsThe use of ANDSystem, Pathway Studio and STRING computer tools based on text-mining and database-mining approaches allowed us to reconstruct associative networks, representing molecular genetic interactions between genes, associated concurrently with comorbid disease pairs, including pre-eclampsia, diabetes mellitus, gestational diabetes and obesity. It was found that these associative networks statistically differed in the number of genes and interactions between them from those built for randomly chosen pairs of diseases. The associative network connecting all four diseases was composed of 16 genes (PLAT, ADIPOQ, ADRB3, LEPR, HP, TGFB1, TNFA, INS, CRP, CSRP1, IGFBP1, MBL2, ACE, ESR1, SHBG, ADA). Such an analysis allowed us to reveal differential gene risk factors for these diseases, and to propose certain, most probable, theoretical mechanisms of pre-eclampsia development in pregnant women. The mechanisms may include the following pathways: [TGFB1 or TNFA]-[IL1B]-[pre-eclampsia]; [TNFA or INS]-[NOS3]-[pre-eclampsia]; [INS]-[HSPA4 or CLU]-[pre-eclampsia]; [ACE]-[MTHFR]-[pre-eclampsia].ConclusionsFor pre-eclampsia, diabetes mellitus, gestational diabetes and obesity, we showed that the size and connectivity of the associative molecular genetic networks, which describe interactions between comorbid diseases, statistically exceeded the size and connectivity of those built for randomly chosen pairs of diseases. Recently, we have shown a similar result for inversely comorbid diseases. This suggests that comorbid and inversely comorbid diseases have common features concerning structural organization of associative molecular genetic networks.
Highlights
Pre-eclampsia is the most common complication occurring during pregnancy
We used the ANDSystem for the reconstruction of associative networks representing molecular genetic interactions between genes associated with PE, diabetes mellitus (DM), gestational diabetes (GD) and obesity (Ob)
Pre-eclampsia: its association, via comorbid genes, with diabetes mellitus, obesity and gestational diabetes The main goal of the current study was to identify comorbid genes whose dysfunction or mutation represent common risk factors for diseases that are concurrent with PE
Summary
Pre-eclampsia is the most common complication occurring during pregnancy. In the majority of cases, it is concurrent with other pathologies in a comorbid manner (frequent co-occurrences in patients), such as diabetes mellitus, gestational diabetes and obesity. Pre-eclampsia (PE) is the leading cause of maternal and foetal morbidity and mortality It is a pregnancy complication, predominantly occurring after 20-weeks of gestation, as well as in labour, and it is characterized by multiple organ dysfunction syndromes, including the dysfunction of the kidneys, liver, vascular and nervous systems, and the foetoplacental complex [1,2]. Women with a history of PE have 1.79 times the risk of venous thromboembolism, 1.81 times the risk of stroke, 2.16 times the risk of ischemic heart disease and 3.7 times the risk of hypertensive disease, compared with women without PE [5] Far, it remains unclear whether the presence of pathological processes before pregnancy predisposes one to PE, or whether defects in multiple organs and systems, induced by PE, are responsible for the development of extragenital diseases in the future. For asthma, tuberculosis, certain cancers and neurodegenerative diseases, we have shown that inversely comorbid diseases are more closely related to each other at the molecular level in comparison with randomly chosen pairs of diseases [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
