title: Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity.
abstract: BACKGROUND
  Pre-eclampsia (PE) has a familial association, with daughters of women who had PE during pregnancy having more than twice the risk of developing PE themselves. Through genome-wide linkage and genetic association studies in PE-affected families and large population samples, we previously identified the following as positional candidate maternal susceptibility genes for PE; ACVR1, INHA, INHBB, ERAP1, ERAP2, LNPEP, COL4A1 and COL4A2. The aims of this study were to determine mRNA expression levels of previously identified candidate maternal pre-eclampsia susceptibility genes from normotensive and severe PE (SPE) pregnancies and correlate mRNA expression levels with the clinical severity of SPE.
  
  
  METHODS
  Third trimester decidual tissues were collected from both normotensive (n = 21) and SPE pregnancies (n = 24) and mRNA expression levels were determined by real-time PCR. Gene expression was then correlated with several parameters of clinical severity in SPE. Statistical significance was determined by Mann-Whitney U test and Spearman's Correlation.
  
  
  RESULTS
  The data demonstrate significantly increased decidual mRNA expression levels of ACVR1, INHBB, ERAP1, ERAP2, LNPEP, COL4A1 and COL4A2 in SPE (p < 0.05). Increased mRNA expression levels of several genes - INHA, INHBB, COL4A1 and COL4A2 were correlated with earlier onset of PE and earlier delivery of the fetus (p < 0.05).
  
  
  CONCLUSIONS
  These results suggest altered expression of maternal susceptibility genes may play roles in PE development and the course of disease severity.
authors: Department of Perinatal Medicine Pregnancy Research Centre and University of Melbourne, Department of Obstetrics and Gynaecology, Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia. Electronic address: ejyong@student.unimelb.edu.au.
authors: H E J
authors: HE
authors: Yong
authors: Department of Perinatal Medicine Pregnancy Research Centre and University of Melbourne, Department of Obstetrics and Gynaecology, Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia. Electronic address: padma@unimelb.edu.au.
authors: P
authors: P
authors: Murthi
authors: Department of Perinatal Medicine Pregnancy Research Centre and University of Melbourne, Department of Obstetrics and Gynaecology, Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia. Electronic address: aj.borg@thewomens.org.au.
authors: A
authors: A
authors: Borg
authors: Department of Perinatal Medicine Pregnancy Research Centre and University of Melbourne, Department of Obstetrics and Gynaecology, Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia. Electronic address: bill.kalionis@thewomens.org.au.
authors: B
authors: B
authors: Kalionis
authors: Centre for Genetic Origins of Health and Disease, University of Western Australia, 35 Stirling Highway, Crawley 6009, Western Australia, Australia. Electronic address: eric.moses@uwa.edu.au.
authors: E K
authors: EK
authors: Moses
authors: Department of Perinatal Medicine Pregnancy Research Centre and University of Melbourne, Department of Obstetrics and Gynaecology, Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia. Electronic address: s.brennecke@unimelb.edu.au.
authors: S P
authors: SP
authors: Brennecke
authors: Department of Perinatal Medicine Pregnancy Research Centre and University of Melbourne, Department of Obstetrics and Gynaecology, Royal Women's Hospital, Locked Bag 300, Corner Grattan Street and Flemington Road, Parkville 3052, Victoria, Australia. Electronic address: rosemary.keogh@thewomens.org.au.
authors: R J
authors: RJ
authors: Keogh
mesh_terms: D030201:Activin Receptors, Type I / Q000096:biosynthesis; D000328:Adult; D024141:Collagen Type IV / Q000096:biosynthesis; D003656:Decidua / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D028322:Inhibin-beta Subunits / Q000096:biosynthesis*; D007265:Inhibins / Q000096:biosynthesis; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: C547475:COL4A1 protein, human; C502625:COL4A2 protein, human; D024141:Collagen Type IV; C422402:INHBB protein, human; D012333:RNA, Messenger; C094377:inhibin-alpha subunit; D007265:Inhibins; D028322:Inhibin-beta Subunits; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I
keywords: Clinical severity; Decidua; Gene expression; Pre-eclampsia; Susceptibility genes