Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease

Preeclampsia (PE) is a serious complication of pregnancy, which is highly correlated with later life cardiovascular disease (CVD). Many risk factors are common for both diseases, but the contribution of shared genes remains to be determined. In this study, we used an integrative strategy to assess l...

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Main Authors: Johansson, A., Curran, J., Johnson, M., Freed, K., Fenstad, M., Bjørge, L., Eide, I., Carless, M., Rainwater, D., Goring, H., Austgulen, R., Moses, Eric, Blangero, J.
Format: Journal Article
Published: 2011
Online Access:http://hdl.handle.net/20.500.11937/37489
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author Johansson, A.
Curran, J.
Johnson, M.
Freed, K.
Fenstad, M.
Bjørge, L.
Eide, I.
Carless, M.
Rainwater, D.
Goring, H.
Austgulen, R.
Moses, Eric
Blangero, J.
author_facet Johansson, A.
Curran, J.
Johnson, M.
Freed, K.
Fenstad, M.
Bjørge, L.
Eide, I.
Carless, M.
Rainwater, D.
Goring, H.
Austgulen, R.
Moses, Eric
Blangero, J.
author_sort Johansson, A.
building Curtin Institutional Repository
collection Online Access
description Preeclampsia (PE) is a serious complication of pregnancy, which is highly correlated with later life cardiovascular disease (CVD). Many risk factors are common for both diseases, but the contribution of shared genes remains to be determined. In this study, we used an integrative strategy to assess lipid traits as risk factors for PE and CVD by whole genome transcriptional profiling performed on Norwegian decidua basalis tissues (N=95) from preeclamptic and normal pregnancies and on blood lymphocytes (N=1240) from the San Antonio Family Heart Study (SAFHS). Among 222 genes that were differentially expressed (false discovery rate (FDR) P-value <0.05) between the PE, cases and controls, we found one gene, ACOX2 (acyl-coenzyme A oxidase 2, branched chain), that was downregulated in PE whose transcription was also inversely correlated with triglyceride levels (P=5.6 × 10−7; FDR P-value=0.0002) in SAFHS. We further report associations between SNPs in the ACOX2 gene and the transcription level (P-value=0.0045) of the gene, as well as with triglyceride levels (P-value=0.0051). ACOX2 is involved in bile acid production, a process that has been associated with both oxidative stress and regulation of triglyceride levels. Oxidative stress and increased triglyceride levels are known risk factors for CVD and both have also been associated with PE. Our results suggest that downregulation of ACOX2 is a shared risk factor for PE and CVD.
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spelling curtin-20.500.11937-374892017-09-13T13:42:27Z Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease Johansson, A. Curran, J. Johnson, M. Freed, K. Fenstad, M. Bjørge, L. Eide, I. Carless, M. Rainwater, D. Goring, H. Austgulen, R. Moses, Eric Blangero, J. Preeclampsia (PE) is a serious complication of pregnancy, which is highly correlated with later life cardiovascular disease (CVD). Many risk factors are common for both diseases, but the contribution of shared genes remains to be determined. In this study, we used an integrative strategy to assess lipid traits as risk factors for PE and CVD by whole genome transcriptional profiling performed on Norwegian decidua basalis tissues (N=95) from preeclamptic and normal pregnancies and on blood lymphocytes (N=1240) from the San Antonio Family Heart Study (SAFHS). Among 222 genes that were differentially expressed (false discovery rate (FDR) P-value <0.05) between the PE, cases and controls, we found one gene, ACOX2 (acyl-coenzyme A oxidase 2, branched chain), that was downregulated in PE whose transcription was also inversely correlated with triglyceride levels (P=5.6 × 10−7; FDR P-value=0.0002) in SAFHS. We further report associations between SNPs in the ACOX2 gene and the transcription level (P-value=0.0045) of the gene, as well as with triglyceride levels (P-value=0.0051). ACOX2 is involved in bile acid production, a process that has been associated with both oxidative stress and regulation of triglyceride levels. Oxidative stress and increased triglyceride levels are known risk factors for CVD and both have also been associated with PE. Our results suggest that downregulation of ACOX2 is a shared risk factor for PE and CVD. 2011 Journal Article http://hdl.handle.net/20.500.11937/37489 10.1038/ejhg.2011.19 unknown
spellingShingle Johansson, A.
Curran, J.
Johnson, M.
Freed, K.
Fenstad, M.
Bjørge, L.
Eide, I.
Carless, M.
Rainwater, D.
Goring, H.
Austgulen, R.
Moses, Eric
Blangero, J.
Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease
title Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease
title_full Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease
title_fullStr Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease
title_full_unstemmed Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease
title_short Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease
title_sort identification of acox2 as a shared genetic risk factor for preeclampsia and cardiovascular disease
url http://hdl.handle.net/20.500.11937/37489