Details of Disease

General Information of Disease (ID: DISY7Q29)

• Disease Name: Pre-eclampsia
• Synonyms: toxemia of pregnancy; toxaemia of pregnancy; pre-eclampsia; preeclampsia/eclampsia; pre-eclamptic toxemia; pregnancy associated hypertension; preeclampsia; proteinuric hypertension of pregnancy; pre-eclamptic toxaemia; gestational hypertension; pregnancy toxemia; hypertension induced by pregnancy; pregnancy toxaemia
• Disease Class: JA24: Pre-eclampsia
• Definition: Preeclampsia is a hypertensive disorder of pregnancy that is characterized by new-onset hypertension with proteinuria presenting after 20 weeks of gestation, and depending on mild or severe forms may initially present with severe headache, visual disturbances, and hyperreflexia.
• Disease Hierarchy:
  DISYKSRF: Genetic disease
  DISVCIJW: Morning sickness
  DISY7Q29: Pre-eclampsia
• ICD Code:
  ICD-11: ICD-11: JA24
  ICD-10: ICD-10: O14, O14.9
  Expand ICD-11: 'JA24
  Expand ICD-10: 'O14; 'O14.9
  Expand ICD-9: 642
• Disease Identifiers:
  MONDO ID: MONDO_0005081
  MESH ID: D011225
  UMLS CUI: C0032914
  MedGen ID: 18608
  HPO ID: HP:0100602
  Orphanet ID: 275555
  SNOMED CT ID: 398254007

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Digibind	DMRJTYV	Phase 2b	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 44 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ADM	TTV14YH	Limited	Altered Expression	[2]
AGT	TT5C0UB	Limited	Genetic Variation	[3]
AKR1C3	TT5ZWB6	Limited	Therapeutic	[4]
C3	TTJGY7A	Limited	Therapeutic	[5]
CCL5	TT9DWLC	Limited	Biomarker	[6]
CD40LG	TTIJP3Q	Limited	Therapeutic	[7]
COMT	TTKWFB8	Limited	Biomarker	[8]
CYP2J2	TTNE1C7	Limited	Biomarker	[9]
IDO1	TTZJYKH	Limited	Biomarker	[10]
ITGA4	TTJMF9P	Limited	Biomarker	[11]
PDE5A	TTJ0IQB	Limited	Biomarker	[12]
PTGS1	TT8NGED	Limited	Biomarker	[13]
TLR3	TTD24Y0	Limited	Biomarker	[14]
CYP11B2	TT9MNE2	moderate	Biomarker	[15]
EDN1	TTJR60Z	moderate	Biomarker	[16]
ENG	TTB30LE	moderate	Therapeutic	[17]
ACVR2A	TTX2DRI	Strong	Genetic Variation	[18]
ADORA2B	TTNE7KG	Strong	Altered Expression	[19]
AGTR1	TT8DBY3	Strong	Biomarker	[20]
ANXA5	TT2Z83I	Strong	Therapeutic	[21]
BDKRB2	TTGY8IW	Strong	Biomarker	[22]
CGB3	TTUH273	Strong	Altered Expression	[23]
CHRNA7	TTLA931	Strong	Altered Expression	[24]
F5	TT1O264	Strong	Genetic Variation	[25]
FGF14	TTKJX1V	Strong	Genetic Variation	[26]
FLT1	TT1VAUK	Strong	SusceptibilityMutation	[27]
HDC	TTV9GOF	Strong	Altered Expression	[28]
HMOX1	TTI6V2A	Strong	Biomarker	[29]
ICAM1	TTA1L39	Strong	Therapeutic	[30]
IFNGR2	TT13TL0	Strong	Altered Expression	[31]
IL16	TTW4R0B	Strong	Altered Expression	[32]
INHBA	TTVB30D	Strong	Biomarker	[33]
LEP	TTBJEZ5	Strong	Biomarker	[34]
LEPR	TT0HD6V	Strong	Genetic Variation	[35]
NOS3	TTCM4B3	Strong	Therapeutic	[36]
PGF	TT48I1Y	Strong	Biomarker	[37]
PLAC1	TTM18HX	Strong	Biomarker	[38]
PRCP	TTTJZ4M	Strong	Genetic Variation	[39]
PYGM	TTZHY6R	Strong	Altered Expression	[40]
SERPIND1	TT8XSKJ	Strong	Altered Expression	[41]
SERPINE1	TTTO43N	Strong	Biomarker	[42]
TDO2	TTXNCBV	Strong	Altered Expression	[43]
TPBG	TT70MLA	Strong	Altered Expression	[44]
IGFBP1	TTCJTWF	Definitive	Biomarker	[45]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
EPHX1	DELB4KP	moderate	Genetic Variation	[46]

This Disease Is Related to 24 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ASB4	OTI4AFZL	Limited	Biomarker	[47]
ERVW-1	OTWV8DXJ	moderate	Altered Expression	[48]
ACE	OTDF1964	Strong	Genetic Variation	[49]
ARHGAP45	OTL86FEQ	Strong	Biomarker	[50]
BOK	OTDQPDIX	Strong	Biomarker	[51]
CORIN	OT4SK7DK	Strong	SusceptibilityMutation	[52]
CP	OTM8JE4Y	Strong	Biomarker	[42]
DDAH2	OT8Q40G2	Strong	Biomarker	[53]
EBAG9	OTTQLQCP	Strong	Altered Expression	[54]
EFNA1	OTU2NUA2	Strong	Altered Expression	[55]
GCM1	OT5CPAUT	Strong	Altered Expression	[56]
GH2	OT32TR4C	Strong	Biomarker	[57]
INHA	OT7HWCO3	Strong	Genetic Variation	[58]
LGALS13	OTEV3DD7	Strong	Altered Expression	[59]
LIPC	OTZY5SC9	Strong	Genetic Variation	[60]
MYCBP2	OTHODA1F	Strong	Genetic Variation	[26]
NPHS1	OT21JD3P	Strong	Altered Expression	[61]
PROZ	OTI3TXBE	Strong	Biomarker	[62]
PSG5	OTHTU98X	Strong	Altered Expression	[44]
SCNN1A	OTE2KVZV	Strong	Biomarker	[63]
SERBP1	OTZVSU0X	Strong	Genetic Variation	[64]
STOX1	OTED3YVO	Strong	SusceptibilityMutation	[65]
SYNPO	OTICDJAB	Strong	Altered Expression	[61]
TAC3	OTOJGM38	Strong	Altered Expression	[66]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Increased adrenomedullin protein content and mRNA expression in human fetal membranes but not placental tissue in pre-eclampsia.Mol Hum Reprod. 2006 Mar;12(3):181-6. doi: 10.1093/molehr/gal016. Epub 2006 Mar 3.
• [3] The angiotensinogen gene M235T polymorphism and development of preeclampsia/eclampsia: a meta-analysis and meta-regression of observational studies.J Hypertens. 2008 Sep;26(9):1726-34. doi: 10.1097/HJH.0b013e3283009ca5.
• [4] [Effects of AKR1C3 on kidney damage of preeclamptic rats].Zhonghua Yi Xue Za Zhi. 2015 Jan 6;95(1):30-3.
• [5] Complement activation is critical for placental ischemia-induced hypertension in the rat. Mol Immunol. 2013 Nov;56(1-2):91-7.
• [6] Immunosuppression improves blood pressure and endothelial function in a rat model of pregnancy-induced hypertension.Am J Hypertens. 2009 Oct;22(10):1107-14. doi: 10.1038/ajh.2009.125. Epub 2009 Jul 16.
• [7] Blockade of CD40 ligand for intercellular communication reduces hypertension, placental oxidative stress, and AT1-AA in response to adoptive transfer of CD4+ T lymphocytes from RUPP rats.Am J Physiol Regul Integr Comp Physiol. 2015 Nov 15;309(10):R1243-50. doi: 10.1152/ajpregu.00273.2015. Epub 2015 Aug 26.
• [8] Deficiency in catechol-O-methyltransferase and 2-methoxyoestradiol is associated with pre-eclampsia.Nature. 2008 Jun 19;453(7198):1117-21. doi: 10.1038/nature06951. Epub 2008 May 11.
• [9] Cytochrome P450 subfamily 2J polypeptide 2 expression and circulating epoxyeicosatrienoic metabolites in preeclampsia.Circulation. 2012 Dec 18;126(25):2990-9. doi: 10.1161/CIRCULATIONAHA.112.127340. Epub 2012 Nov 15.
• [10] Pregnant mice lacking indoleamine 2,3-dioxygenase exhibit preeclampsia phenotypes.Physiol Rep. 2015 Jan 19;3(1):e12257. doi: 10.14814/phy2.12257. Print 2015 Jan 1.
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• [18] Association between the candidate susceptibility gene ACVR2A on chromosome 2q22 and pre-eclampsia in a large Norwegian population-based study (the HUNT study).Eur J Hum Genet. 2009 Feb;17(2):250-7. doi: 10.1038/ejhg.2008.158. Epub 2008 Sep 10.
• [19] Human equilibrative nucleoside transporters 1 and 2 may be differentially modulated by A2B adenosine receptors in placenta microvascular endothelial cells from pre-eclampsia.Placenta. 2008 Sep;29(9):816-25. doi: 10.1016/j.placenta.2008.06.014. Epub 2008 Aug 13.
• [20] Prevalence of agonistic autoantibodies against the angiotensin II type 1 receptor and soluble fms-like tyrosine kinase 1 in a gestational age-matched case study.Hypertension. 2009 Feb;53(2):393-8. doi: 10.1161/HYPERTENSIONAHA.108.124115. Epub 2008 Dec 8.
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• [23] Elevated levels of b-human chorionic gonadotropin and human placental lactogen between 11-13 weeks' gestation and subsequent pregnancy complications in Omani women.Saudi Med J. 2004 Mar;25(3):382-4.
• [24] Difference in the expression of alpha 7 nicotinic receptors in the placenta in normal versus severe preeclampsia pregnancies.Eur J Obstet Gynecol Reprod Biol. 2007 May;132(1):35-9. doi: 10.1016/j.ejogrb.2006.05.034. Epub 2006 Jul 11.
• [25] Ethnic differences in the association of factor V Leiden mutation and the C677T methylenetetrahydrofolate reductase gene polymorphism with preeclampsia.Eur J Obstet Gynecol Reprod Biol. 2004 Feb 10;112(2):162-9. doi: 10.1016/s0301-2115(03)00314-2.
• [26] Genome-wide association study of pre-eclampsia detects novel maternal single nucleotide polymorphisms and copy-number variants in subsets of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study cohort.Ann Hum Genet. 2013 Jul;77(4):277-87. doi: 10.1111/ahg.12021. Epub 2013 Apr 2.
• [27] Variants in the fetal genome near FLT1 are associated with risk of preeclampsia.Nat Genet. 2017 Aug;49(8):1255-1260. doi: 10.1038/ng.3895. Epub 2017 Jun 19.
• [28] Differential activity of histidine decarboxylase in normal and pre-eclamptic placentae.Placenta. 2007 May-Jun;28(5-6):585-7. doi: 10.1016/j.placenta.2006.05.003. Epub 2006 Jul 5.
• [29] Resveratrol inhibits the release of soluble fms-like tyrosine kinase (sFlt-1) from human placenta.Am J Obstet Gynecol. 2012 Mar;206(3):253.e10-5. doi: 10.1016/j.ajog.2011.11.010. Epub 2011 Nov 25.
• [30] Monoclonal antibody to intercellular adhesion molecule-1 as a novel therapy for preeclampsia: preliminary results from a rat model.J Matern Fetal Neonatal Med. 2012 Jun;25(6):855-9. doi: 10.3109/14767058.2011.599077. Epub 2011 Aug 10.
• [31] Placental expression of interferon-gamma (IFN-gamma) and its receptor IFN-gamma R2 fail to switch from early hypoxic to late normotensive development in preeclampsia.J Clin Endocrinol Metab. 2005 Feb;90(2):944-52. doi: 10.1210/jc.2004-1113. Epub 2004 Dec 7.
• [32] Elevated maternal IL-16 levels, enhanced IL-16 expressions in endothelium and leukocytes, and increased IL-16 production by placental trophoblasts in women with preeclampsia.J Immunol. 2008 Sep 15;181(6):4418-22. doi: 10.4049/jimmunol.181.6.4418.
• [33] Oxidative stress increases placental and endothelial cell activin A secretion.J Endocrinol. 2007 Mar;192(3):485-93. doi: 10.1677/JOE-06-0061.
• [34] Circulating leptin and angiogenic factors in preeclampsia patients.Endocr J. 2008 Jul;55(3):565-73. doi: 10.1507/endocrj.k07e-136. Epub 2008 May 20.
• [35] Leptin receptor gene polymorphisms in severely pre-eclamptic women.Gynecol Endocrinol. 2006 Sep;22(9):521-5. doi: 10.1080/01674820600915502.
• [36] Apelin as a novel drug for treating preeclampsia.Exp Ther Med. 2017 Dec;14(6):5917-5923. doi: 10.3892/etm.2017.5304. Epub 2017 Oct 13.
• [37] Contribution of angiogenic factors in a rat model of pre-eclampsia.Am J Nephrol. 2010;32(4):332-9. doi: 10.1159/000319463. Epub 2010 Aug 19.
• [38] Cell-free mRNA concentrations of CRH, PLAC1, and selectin-P are increased in the plasma of pregnant women with preeclampsia.Prenat Diagn. 2007 Aug;27(8):772-7. doi: 10.1002/pd.1780.
• [39] Prolylcarboxypeptidase gene, chronic hypertension, and risk of preeclampsia.Am J Obstet Gynecol. 2006 Jul;195(1):162-71. doi: 10.1016/j.ajog.2006.01.079. Epub 2006 May 8.
• [40] cDNA microarray analysis of gene expression profiles in human placenta: up-regulation of the transcript encoding muscle subunit of glycogen phosphorylase in preeclampsia.J Soc Gynecol Investig. 2003 Dec;10(8):496-502. doi: 10.1016/s1071-5576(03)00154-0.
• [41] Placental dermatan sulfate: isolation, anticoagulant activity, and association with heparin cofactor II.Blood. 2006 Apr 1;107(7):2753-8. doi: 10.1182/blood-2005-09-3755. Epub 2005 Dec 8.
• [42] Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia.Lab Invest. 2008 Oct;88(10):1057-67. doi: 10.1038/labinvest.2008.74. Epub 2008 Aug 4.
• [43] Decreased tryptophan catabolism by placental indoleamine 2,3-dioxygenase in preeclampsia.Am J Obstet Gynecol. 2003 Mar;188(3):719-26. doi: 10.1067/mob.2003.156.
• [44] Placenta-derived, cellular messenger RNA expression in the maternal blood of preeclamptic women.Obstet Gynecol. 2007 Nov;110(5):1130-6. doi: 10.1097/01.AOG.0000286761.11436.67.
• [45] Changes in circulating level of IGF-I and IGF-binding protein-1 from the first to second trimester as predictors of preeclampsia.Eur J Endocrinol. 2008 Jan;158(1):101-5. doi: 10.1530/EJE-07-0386.
• [46] Association of microsomal epoxide hydrolase gene polymorphism and pre-eclampsia in Turkish women.J Obstet Gynaecol Res. 2007 Feb;33(1):32-7. doi: 10.1111/j.1447-0756.2007.00473.x.
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• [48] Hypoxia alters expression and function of syncytin and its receptor during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in pre-eclampsia.Biochim Biophys Acta. 2003 May 20;1638(1):63-71. doi: 10.1016/s0925-4439(03)00043-7.
• [49] Association of angiotensin-converting enzyme insertion-deletion polymorphism with preeclampsia.Coll Antropol. 2008 Jun;32(2):339-43.
• [50] Trophoblast expression of the minor histocompatibility antigen HA-1 is regulated by oxygen and is increased in placentas from preeclamptic women.Placenta. 2015 Aug;36(8):832-8. doi: 10.1016/j.placenta.2015.05.018. Epub 2015 Jun 6.
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• [52] Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy. Nature. 2012 Mar 21;484(7393):246-50. doi: 10.1038/nature10897.
• [53] Severely decreased activity of placental dimethylarginine dimethylaminohydrolase in pre-eclampsia.Eur J Obstet Gynecol Reprod Biol. 2012 Apr;161(2):152-6. doi: 10.1016/j.ejogrb.2011.12.032. Epub 2012 Jan 28.
• [54] RCAS1 decidual immunoreactivity in severe pre-eclampsia: immune cell presence and activity.Am J Reprod Immunol. 2007 Oct;58(4):358-66. doi: 10.1111/j.1600-0897.2007.00521.x.
• [55] Eph and ephrin expression in normal placental development and preeclampsia.Placenta. 2004 Aug;25(7):623-30. doi: 10.1016/j.placenta.2004.01.016.
• [56] Increased plasma mRNAs of placenta-specific 1 (PLAC1) and glial cells-missing 1 (GCM1) in mothers with pre-eclampsia.Hiroshima J Med Sci. 2006 Mar;55(1):9-15.
• [57] Placental growth hormone is increased in the maternal and fetal serum of patients with preeclampsia.J Matern Fetal Neonatal Med. 2007 Sep;20(9):651-9. doi: 10.1080/14767050701463571.
• [58] The 769G>A variant of the inhibin-alpha gene in Korean patients with preeclampsia.J Endocrinol Invest. 2008 Aug;31(8):700-3. doi: 10.1007/BF03346418.
• [59] Placental protein 13 (galectin-13) has decreased placental expression but increased shedding and maternal serum concentrations in patients presenting with preterm pre-eclampsia and HELLP syndrome.Virchows Arch. 2008 Oct;453(4):387-400. doi: 10.1007/s00428-008-0658-x. Epub 2008 Sep 13.
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• [65] STOX1: Key player in trophoblast dysfunction underlying early onset preeclampsia with growth retardation.J Pregnancy. 2011;2011:521826. doi: 10.1155/2011/521826. Epub 2010 Dec 15.
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