H E J Yong1, P Murthi2, A Borg3, B Kalionis4, E K Moses5, S P Brennecke6, R J Keogh7. 1. 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. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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.
Abstract
INTRODUCTION: 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). CONCLUSION: These results suggest altered expression of maternal susceptibility genes may play roles in PE development and the course of disease severity.
INTRODUCTION: 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). CONCLUSION: These results suggest altered expression of maternal susceptibility genes may play roles in PE development and the course of disease severity.
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