Preeclampsia and Related Cardiovascular Risk: Common Genetic Background.
Ontology highlight
ABSTRACT:
SUBMITTER: Lisowska M
PROVIDER: S-EPMC6028827 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
Publications
Preeclampsia and Related Cardiovascular Risk: Common Genetic Background.
Lisowska Michalina M Pietrucha Tadeusz T Sakowicz Agata A
Current hypertension reports 20180703 8
<h4>Purpose of review</h4>Preeclampsia (PE) is a hypertensive disorder exclusive for pregnancy. It affects women all over the world and poses a great threat to life, both for mother and child. No definitive treatment exists and placenta delivery comprises the only known cure for PE. One of the most severe complications observed in preeclamptic women is the occurrence of cardiovascular diseases (CVDs) later in life.<h4>Recent findings</h4>Both PE and CVDs share some of their pathogenic pathways a ...[more]
Similar Datasets
Project 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.
| S-EPMC3137494 | biostudies-literature
Project description:Clustering of obesity, coronary artery disease, and cardiovascular disease risk factors is observed in epidemiological studies and clinical settings. Twin and family studies have provided some supporting evidence for the clustering hypothesis. Loci nearest a lead single nucleotide polymorphism (SNP) showing genome-wide significant associations with coronary artery disease, body mass index, C-reactive protein, blood pressure, lipids, and type 2 diabetes mellitus were selected for pathway and network analyses. Eighty-seven autosomal regions (181 SNPs), mapping to 56 genes, were found to be pleiotropic. Most pleiotropic regions contained genes associated with coronary artery disease and plasma lipids, whereas some exhibited coaggregation between obesity and cardiovascular disease risk factors. We observed enrichment for liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor/RXR nuclear receptor signaling among pleiotropic genes and for signatures of coronary artery disease and hepatic steatosis. In the search for functionally interacting networks, we found that 43 pleiotropic genes were interacting in a network with an additional 24 linker genes. ENCODE (Encyclopedia of DNA Elements) data were queried for distribution of pleiotropic SNPs among regulatory elements and coding sequence variations. Of the 181 SNPs, 136 were annotated to ≥ 1 regulatory feature. An enrichment analysis found over-representation of enhancers and DNAse hypersensitive regions when compared against all SNPs of the 1000 Genomes pilot project. In summary, there are genomic regions exerting pleiotropic effects on cardiovascular disease risk factors, although only a few included obesity. Further studies are needed to resolve the clustering in terms of DNA variants, genes, pathways, and actionable targets.
| S-EPMC4416656 | biostudies-literature
Project description:Background There is increased risk of hypertension, early cardiovascular disease, and premature mortality in women who have had preeclampsia. This study was undertaken to determine the upper limit of normal blood pressure (BP) 6 months postpartum and the frequency of women with prior preeclampsia who had BP above these limits, as part of the P4 (Post-Partum Physiology, Psychology and Pediatric) follow-up study. Methods and Results BP was measured by sphygmomanometer, 24-hour ambulatory BP monitoring, and non-invasive central BP at 6 months postpartum in 302 women who had normotensive pregnancy and 90 who had preeclampsia. The upper limit of normal BP (mean+2 SD) for women with normotensive pregnancy was 122/79 mm Hg for routine BP, 115/81 mm Hg for central BP, and 121/78 mm Hg for 24-hour ambulatory BP monitoring. Traditional normal values detected only 3% of women who had preeclampsia as having high BP 6 months postpartum whereas these new values detected between 13% and 19%. Women with preeclampsia had greater body mass index (27.8 versus 25.0, P<0.001) and left ventricular wall thickness but similar augmentation index. They also had lower high-density lipoprotein (59±15 versus 65±16 mg/dL, P=0.002), higher triglycerides (77±51 versus 61±35 mg/dL, P=0.005), and higher homeostatic model assessment score (2.1±1.8 versus 1.3±1.9, P<0.001). Conclusions Clinicians wishing to detect high BP in these women should be aware of the lower than usual upper limit of normal for this young cohort and where possible should use 24-hour ambulatory BP monitoring to detect these changes. This may define a subgroup of women who had preeclampsia for whom targeted BP lowering therapy would be successful. Registration URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365295&isReview=true; Unique identifier: ACTRN12613001260718.
| S-EPMC7763721 | biostudies-literature
Project description:The relationship between obesity, diabetes, hyperlipidemia, hypertension, kidney disease and cardiovascular disease (CVD) is established when looked at from a clinical, epidemiological or pathophysiological perspective. Yet, when viewed from a genetic perspective, there is comparatively little data synthesis that these conditions have an underlying relationship. We sought to investigate the overlap of genetic variants independently associated with each of these commonly co-existing conditions from the NHGRI genome-wide association study (GWAS) catalog, in an attempt to replicate the established notion of shared pathophysiology and risk. We used pathway-based analyses to detect subsets of pleiotropic genes involved in similar biological processes. We identified 107 eligible GWAS studies related to CVD and its established comorbidities and risk factors and assigned genes that correspond to the associated signals based on their position. We found 44 positional genes shared across at least two CVD-related phenotypes that independently recreated the established relationship between the six phenotypes, but only if studies representing non-European populations were included. Seven genes revealed pleiotropy across three or more phenotypes, mostly related to lipid transport and metabolism. Yet, many genes had no relationship to each other or to genes with established functional connection. Whilst we successfully reproduced established relationships between CVD risk factors using GWAS findings, interpretation of biological pathways involved in the observed pleiotropy was limited. Further studies linking genetic variation to gene expression, as well as describing novel biological pathways will be needed to take full advantage of GWAS results.
| S-EPMC3460880 | biostudies-literature
Project description:BACKGROUND:Epidemiologic studies have shown consistent associations between obesity and increased thyroid cancer risk, but, to date, no studies have investigated the relationship between thyroid cancer risk and obesity-related single-nucleotide polymorphisms (SNP). METHODS:We evaluated 575 tag SNPs in 23 obesity-related gene regions in a case-control study of 341 incident papillary thyroid cancer (PTC) cases and 444 controls of European ancestry. Logistic regression models, adjusted for attained age, year of birth, and sex were used to calculate ORs and 95% confidence intervals (CI) with SNP genotypes, coded as 0, 1, and 2 and modeled continuously to calculate P(trend). RESULTS:Nine of 10 top-ranking SNPs (P(trend) < 0.01) were located in the FTO (fat mass and obesity associated) gene region, whereas the other was located in INSR (insulin receptor). None of the associations were significant after correcting for multiple testing. CONCLUSIONS:Our data do not support an important role of obesity-related genetic polymorphisms in determining the risk of PTC. IMPACT:Factors other than selected genetic polymorphisms may be responsible for the observed associations between obesity and increased PTC risk.
| S-EPMC3518668 | biostudies-literature
Project description:The association between spondyloarthropathy and inflammatory bowel disease (IBD) is largely established, although prevalence is variable because of different population selection and diagnostic methodologies. Most studies indicate that as many as 10%-15% of cases of IBD are complicated by ankylosing spondylitis (AS) or other forms of spondylarthritis (SpA). Of note, ileal inflammation resembling IBD has been reported in up to two thirds of cases of SpA, and it has been suggested that the presence of ileitis is associated with the chronicity of articular complications. Although this observation is of interest to unravel the pathophysiology of the disease, systematic screening of patients with SpA by ileocolonoscopy is not indicated in the absence of gut symptoms, as only a small proportion of patients with subclinical gut inflammation will develop overt IBD over time. The existence of familial clustering of both IBD and AS, the coexistence of both conditions in a patient, the evidence of an increased risk ratio among first- and second-degree relatives of affected AS or IBD patients and finally, the increased cross-risk ratios between AS and IBD, strongly suggest a shared genetic background. So far, however, IL23R is the only identified susceptibility gene shared by both IBD and AS. Although functional studies are still needed to better understand its pathogenic role, great effort is being spent therapeutically targeting this pathway that may prove effective for both disorders.
| S-EPMC2686902 | biostudies-literature
Project description:ImportancePreeclampsia is an independent risk factor for future cardiovascular disease and disproportionally affects non-Hispanic Black women. The association of maternal nativity and duration of US residence with preeclampsia and other cardiovascular risk factors is well described among non-Hispanic Black women but not among women of other racial and ethnic groups.ObjectiveTo examine differences in cardiovascular risk factors and preeclampsia prevalence by race and ethnicity, nativity, and duration of US residence among Hispanic, non-Hispanic Black, and non-Hispanic White women.Design, setting, and participantsThis cross-sectional analysis of the Boston Birth Cohort included a racially diverse cohort of women who had singleton deliveries at the Boston Medical Center from October 1, 1998, to February 15, 2016. Participants self-identified as Hispanic, non-Hispanic Black, or non-Hispanic White. Data were analyzed from March 1 to March 31, 2021.ExposuresMaternal nativity and duration of US residence (<10 vs ≥10 years) were self-reported.Main outcome and measuresDiagnosis of preeclampsia, the outcome of interest, was retrieved from maternal medical records.ResultsA total of 6096 women (2400 Hispanic, 2699 non-Hispanic Black, and 997 non-Hispanic White) with a mean (SD) age of 27.5 (6.3) years were included in the study sample. Compared with Hispanic and non-Hispanic White women, non-Hispanic Black women had the highest prevalence of chronic hypertension (204 of 2699 [7.5%] vs 65 of 2400 [2.7%] and 28 of 997 [2.8%], respectively), obesity (658 of 2699 [24.4%] vs 380 of 2400 [15.8%] and 152 of 997 [15.2%], respectively), and preeclampsia (297 of 2699 [11.0%] vs 212 of 2400 [8.8%] and 71 of 997 [7.1%], respectively). Compared with their counterparts born outside the US, US-born women in all 3 racial and ethnic groups had a significantly higher prevalence of obesity (Hispanic women, 132 of 556 [23.7%] vs 248 of 1844 [13.4%]; non-Hispanic Black women, 444 of 1607 [27.6%] vs 214 of 1092 [19.6%]; non-Hispanic White women, 132 of 776 [17.0%] vs 20 of 221 [9.0%]), smoking (Hispanic women, 98 of 556 [17.6%] vs 30 of 1844 [1.6%]; non-Hispanic Black women, 330 of 1607 [20.5%] vs 53 of 1092 [4.9%]; non-Hispanic White women, 382 of 776 [49.2%] vs 42 of 221 [19.0%]), and severe stress (Hispanic women, 76 of 556 [13.7%] vs 85 of 1844 [4.6%]; non-Hispanic Black women, 231 of 1607 [14.4%] vs 120 of 1092 [11.0%]; non-Hispanic White women, 164 of 776 [21.1%] vs 26 of 221 [11.8%]). After adjusting for sociodemographic and cardiovascular risk factors, birth status outside the US (adjusted odds ratio [aOR], 0.74 [95% CI, 0.55-1.00]) and shorter duration of US residence (aOR, 0.62 [95% CI, 0.41-0.93]) were associated with lower odds of preeclampsia among non-Hispanic Black women. However, among Hispanic and non-Hispanic White women, maternal nativity (aOR for Hispanic women, 1.07 [95% CI, 0.72-1.60]; aOR for non-Hispanic White women, 0.98 [95% CI, 0.49-1.96]) and duration of US residence (aOR for Hispanic women <10 years, 1.04 [95% CI, 0.67-1.59]; aOR for non-Hispanic White women <10 years, 1.20 [95% CI, 0.48-3.02]) were not associated with preeclampsia.Conclusions and relevanceNativity-related disparities in preeclampsia persisted among non-Hispanic Black women but not among Hispanic and non-Hispanic White women after adjusting for sociodemographic and cardiovascular risk factors. Further research is needed to explore the interplay of factors contributing to nativity-related disparities in preeclampsia, particularly among non-Hispanic Black women.
| S-EPMC8689384 | biostudies-literature
Project description:Calcium oxalate (CaOx) crystal formation, aggregation and growth is a common cause of kidney stone disease and nephrocalcinosis-related chronic kidney disease (CKD). Genetically modified mouse strains are frequently used as an experimental tool in this context but observed phenotypes may also relate to the genetic background or intestinal microbiota. We hypothesized that the genetic background or intestinal microbiota of mice determine CaOx crystal deposition and thus the outcome of nephrocalcinosis. Indeed, Casp1 -/-, Cybb -/- or Casp1 -/-/Cybb -/- knockout mice on a 129/C57BL/6J (B6J) background that were fed an oxalate-rich diet for 14 days did neither encounter intrarenal CaOx crystal deposits nor nephrocalcinosis-related CKD. To test our assumption, we fed C57BL/6N (B6N), 129, B6J and Balb/c mice an oxalate-rich diet for 14 days. Only B6N mice displayed CaOx crystal deposits and developed CKD associated with tubular injury, inflammation and interstitial fibrosis. Intrarenal mRNA expression profiling of 64 known nephrocalcinosis-related genes revealed that healthy B6N mice had lower mRNA levels of uromodulin (Umod) compared to the other three strains. Feeding an oxalate-rich diet caused an increase in uromodulin protein expression and CaOx crystal deposition in the kidney as well as in urinary uromodulin excretion in B6N mice but not 129, B6J and Balb/c mice. However, backcrossing 129 mice on a B6N background resulted in a gradual increase in CaOx crystal deposits from F2 to F7, of which all B6N/129 mice from the 7th generation developed CaOx-related nephropathy similar to B6N mice. Co-housing experiments tested for a putative role of the intestinal microbiota but B6N co-housed with 129 mice or B6N/129 (3rd and 6th generation) mice did not affect nephrocalcinosis. In summary, genetic background but not the intestinal microbiome account for strain-specific crystal formation and, the levels of uromodulin secretion may contribute to this phenomenon. Our results imply that only littermate controls of the identical genetic background strain are appropriate when performing knockout mouse studies in this context, while co-housing is optional.
| S-EPMC8100042 | biostudies-literature
Project description:BackgroundPreeclampsia is a hypertensive complication of pregnancy characterized by novel onset of hypertension after 20 weeks gestation, accompanied by proteinuria. Epidemiological evidence suggests that genetic susceptibility exists for preeclampsia; however, whether preeclampsia is the result of underlying genetic risk for essential hypertension has yet to be investigated. Based on the hypertensive state that is characteristic of preeclampsia, we aimed to determine if established genetic risk scores (GRSs) for hypertension and blood pressure are associated with preeclampsia.MethodsSubjects consisted of 162 preeclamptic cases and 108 normotensive pregnant controls, all of Iowa residence. Subjects' DNA was extracted from buccal swab samples and genotyped on the Affymetrix Genome-wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA). Missing genotypes were imputed using MaCH and Minimac software. GRSs were calculated for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) using established genetic risk loci for each outcome. Regression analyses were performed to determine the association between GRS and risk of preeclampsia. These analyses were replicated in an independent US population of 516 cases and 1,097 controls of European ancestry.ResultsGRSs for hypertension, SBP, DBP, and MAP were not significantly associated with risk for preeclampsia (P > 0.189). The results of the replication analysis also yielded nonsignificant associations.ConclusionsGRSs for hypertension and blood pressure are not associated with preeclampsia, suggesting that an underlying predisposition to essential hypertension is not on the causal pathway of preeclampsia.
| S-EPMC4692983 | biostudies-literature
Project description:BackgroundLarge epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia.MethodsPreeclampsia cases (n = 164) and normotensive controls (n = 110) were selected from live birth certificates to nulliparous Iowa women during the period August 2002 to May 2005. Disease status was verified by medical chart review. Genetic predisposition to dyslipidemia was estimated by 4 genetic risk scores (GRS) (total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides) on the basis of established loci for blood lipids. Logistic regression analyses were used to evaluate the relationships between each of the 4 genotype scores and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry.ResultsThe GRS related to higher levels of TC, LDL-C, and triglycerides demonstrated no association with the risk of preeclampsia in either the Iowa or replication population. The GRS related to lower HDL-C was marginally associated with an increased risk for preeclampsia (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.99-1.07; P = 0.10). In the independent replication population, the association with the HDL-C GRS was also marginally significant (OR = 1.03, 95% CI: 1.00-1.06; P = 0.04).ConclusionsOur data suggest a potential effect between the genetic predisposition to dyslipidemic levels of HDL-C and an increased risk of preeclampsia, and, as such, suggest that dyslipidemia may be a component along the causal pathway to preeclampsia.
| S-EPMC4542907 | biostudies-literature