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Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease
Asa Johansson1, Joanne E Curran, Matthew P Johnson
1Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. asa.johansson@ucr.uu.se
Insights
Downregulation of the ACOX2 gene is linked to preeclampsia (PE) and later cardiovascular disease (CVD). This gene
Area of Science:
- Genetics and Molecular Biology
- Obstetrics and Gynecology
- Cardiovascular Medicine
Background:
- Preeclampsia (PE) is a pregnancy complication strongly associated with future cardiovascular disease (CVD).
- Shared genetic factors between PE and CVD are not well understood.
- Lipid traits are potential common risk factors for both conditions.
Purpose of the Study:
- To investigate lipid traits as shared risk factors for PE and CVD.
- To identify genes involved in the pathogenesis of PE and their potential link to CVD.
- To explore the role of ACOX2 gene in the development of PE and CVD.
Main Methods:
- Whole genome transcriptional profiling of Norwegian decidua basalis tissues (N=95) from PE and normal pregnancies.
- Analysis of blood lymphocytes (N=1240) from the San Antonio Family Heart Study (SAFHS).
- Identification of differentially expressed genes and association analysis with lipid traits and SNPs.
Main Results:
- One gene, ACOX2 (acyl-coenzyme A oxidase 2, branched chain), was found downregulated in PE.
- ACOX2 transcription inversely correlated with triglyceride levels in SAFHS (P = 5.6 × 10⁻⁷).
- Single nucleotide polymorphisms (SNPs) in ACOX2 associated with gene transcription levels and triglyceride levels.
Conclusions:
- Downregulation of ACOX2 is a potential shared genetic risk factor for PE and CVD.
- ACOX2's role in bile acid production links it to oxidative stress and triglyceride regulation, key factors in both PE and CVD.
- Further research into ACOX2 may reveal therapeutic targets for preventing PE and CVD.
Abstract:
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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