Preeclampsia and Related Cardiovascular Risk: Common Genetic Background.
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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]
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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.
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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.
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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.
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