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Molecular association of pathogenetic contributors to pre-eclampsia (pre-eclampsia associome). 2015

Andrey S Glotov, and Evgeny S Tiys, and Elena S Vashukova, and Vladimir S Pakin, and Pavel S Demenkov, and Olga V Saik, and Timofey V Ivanisenko, and Olga N Arzhanova, and Elena V Mozgovaya, and Marina S Zainulina, and Nikolay A Kolchanov, and Vladislav S Baranov, and Vladimir A Ivanisenko

BACKGROUND 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. 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. RESULTS The 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]. CONCLUSIONS For 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.

UI MeSH Term Description Entries
D009765 Obesity A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
D011225 Pre-Eclampsia A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Toxemias, Pregnancy,EPH Complex,EPH Gestosis,EPH Toxemias,Edema-Proteinuria-Hypertension Gestosis,Gestosis, EPH,Hypertension-Edema-Proteinuria Gestosis,Preeclampsia,Preeclampsia Eclampsia 1,Pregnancy Toxemias,Proteinuria-Edema-Hypertension Gestosis,Toxemia Of Pregnancy,1, Preeclampsia Eclampsia,1s, Preeclampsia Eclampsia,EPH Toxemia,Eclampsia 1, Preeclampsia,Eclampsia 1s, Preeclampsia,Edema Proteinuria Hypertension Gestosis,Gestosis, Edema-Proteinuria-Hypertension,Gestosis, Hypertension-Edema-Proteinuria,Gestosis, Proteinuria-Edema-Hypertension,Hypertension Edema Proteinuria Gestosis,Of Pregnancies, Toxemia,Of Pregnancy, Toxemia,Pre Eclampsia,Preeclampsia Eclampsia 1s,Pregnancies, Toxemia Of,Pregnancy Toxemia,Pregnancy, Toxemia Of,Proteinuria Edema Hypertension Gestosis,Toxemia Of Pregnancies,Toxemia, EPH,Toxemia, Pregnancy,Toxemias, EPH
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D005260 Female Females
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012984 Software Sequential operating programs and data which instruct the functioning of a digital computer. Computer Programs,Computer Software,Open Source Software,Software Engineering,Software Tools,Computer Applications Software,Computer Programs and Programming,Computer Software Applications,Application, Computer Software,Applications Software, Computer,Applications Softwares, Computer,Applications, Computer Software,Computer Applications Softwares,Computer Program,Computer Software Application,Engineering, Software,Open Source Softwares,Program, Computer,Programs, Computer,Software Application, Computer,Software Applications, Computer,Software Tool,Software, Computer,Software, Computer Applications,Software, Open Source,Softwares, Computer Applications,Softwares, Open Source,Source Software, Open,Source Softwares, Open,Tool, Software,Tools, Software
D015897 Comorbidity The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival.
D016640 Diabetes, Gestational Diabetes mellitus induced by PREGNANCY but resolved at the end of pregnancy. It does not include previously diagnosed diabetics who become pregnant (PREGNANCY IN DIABETICS). Gestational diabetes usually develops in late pregnancy when insulin antagonistic hormones peaks leading to INSULIN RESISTANCE; GLUCOSE INTOLERANCE; and HYPERGLYCEMIA. Diabetes Mellitus, Gestational,Diabetes, Pregnancy-Induced,Gestational Diabetes,Diabetes, Pregnancy Induced,Gestational Diabetes Mellitus,Pregnancy-Induced Diabetes
D048909 Diabetes Complications Conditions or pathological processes associated with the disease of diabetes mellitus. Due to the impaired control of BLOOD GLUCOSE level in diabetic patients, pathological processes develop in numerous tissues and organs including the EYE, the KIDNEY, the BLOOD VESSELS, and the NERVE TISSUE. Complications of Diabetes Mellitus,Diabetes-Related Complications,Diabetic Complications,Diabetes Complication,Diabetes Mellitus Complication,Diabetes Mellitus Complications,Diabetes Related Complications,Diabetes-Related Complication,Diabetic Complication

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