Document Detail


Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease.
MedLine Citation:
PMID:  21343950     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Asa Johansson; Joanne E Curran; Matthew P Johnson; Katy A Freed; Mona H Fenstad; Line Bjørge; Irina P Eide; Melanie A Carless; David L Rainwater; Harald H H Goring; Rigmor Austgulen; Eric K Moses; John Blangero
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-23
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  19     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-16     Completed Date:  2011-10-05     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  796-800     Citation Subset:  IM    
Affiliation:
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. asa.johansson@ucr.uu.se
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MeSH Terms
Descriptor/Qualifier:
Acyl-CoA Oxidase / genetics*
Cardiovascular Diseases / genetics*
Case-Control Studies
Female
Gene Expression Profiling
Gene Expression Regulation / genetics
Genome-Wide Association Study
Humans
Leukocytes / metabolism
Lipid Metabolism / genetics
Polymorphism, Single Nucleotide / genetics
Pre-Eclampsia / genetics*
Pregnancy
Risk Factors
Triglycerides / metabolism
Grant Support
ID/Acronym/Agency:
HD049847/HD/NICHD NIH HHS; HL45522/HL/NHLBI NIH HHS; MH59490/MH/NIMH NIH HHS; RR017515/RR/NCRR NIH HHS; RR13556/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Triglycerides; EC 1.3.3.6/Acyl-CoA Oxidase
Comments/Corrections

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