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Meet Teddy Rex
New student Teddy the Tyrannosuarus Rex learns to use his \"inside roar\" inside the classroom.
Book
Genetics of Human Primary Hypertension: Focus on Hormonal Mechanisms
Abstract
Increasingly, primary hypertension is being considered a syndrome and not a disease, with the individual causes (diseases) having a common sign—an elevated blood pressure. To determine these causes, genetic tools are increasingly employed. This review identified 62 proposed genes. However, only 21 of them met our inclusion criteria: (i) primary hypertension, (ii) two or more supporting cohorts from different publications or within a single publication or one supporting cohort with a confirmatory genetically modified animal study, and (iii) 600 or more subjects in the primary cohort; when including our exclusion criteria: (i) meta-analyses or reviews, (ii) secondary and monogenic hypertension, (iii) only hypertensive complications, (iv) genes related to blood pressure but not hypertension per se, (v) nonsupporting studies more common than supporting ones, and (vi) studies that did not perform a Bonferroni or similar multiassessment correction. These 21 genes were organized in a four-tiered structure: distant phenotype (hypertension); intermediate phenotype [salt-sensitive (18) or salt-resistant (0)]; subintermediate phenotypes under salt-sensitive hypertension [normal renin (4), low renin (8), and unclassified renin (6)]; and proximate phenotypes (specific genetically driven hypertensive subgroup). Many proximate hypertensive phenotypes had a substantial endocrine component. In conclusion, primary hypertension is a syndrome; many proposed genes are likely to be false positives; and deep phenotyping will be required to determine the utility of genetics in the treatment of hypertension. However, to date, the positive genes are associated with nearly 50% of primary hypertensives, suggesting that in the near term precise, mechanistically driven treatment and prevention strategies for the specific primary hypertension subgroups are feasible.
Journal Article
Pete can fly!
\"Teddy the T-Rex is jealous that his best friend Pete the Pterodactyl can fly. But when a friend Tina the Tricertaops reminds Teddy of all the great things a T-Rex can do, Teddy ends up feeling much better about himself\"-- Provided by publisher.
Book
Genetic Association of the Renin-Angiotensin-Aldosterone System with hypertension among the Malays and their adaptation to climate change
Hypertension (HT) is a ‘by-product’ to the forces of natural selection against environmental drift and salt availability, therefore contributed to differential HT susceptibility. This study provides further supporting evidence through: (i) associating three salt-sensitive related candidate gene variants, to the susceptibility of HT among the Malays from Peninsular Malaysia with a detail genotype-phenotype evaluation; (ii) comparing the blood pressure and the frequency spectrums of these variants across global populations; (iii) correlating them with the geographical coordinates and BP of the respective populations, and evaluating the presence of local adaptation in these candidate variants. We tested the genetic association of six SNPs underlying CYP11B2 , AGT and ADRB2 in 918 normotensives and hypertensives Malays, men and women. CYP11B2 and ADRB2 were associated with elevated BP in males and females, respectively. Evaluation of these gene variations across 38 populations residing in different latitudinal clines revealed strong correlations between CYP11B2 , AGT and latitudinal coordinates; whilst ADRB2 to a weaker extent. Tajima’s D analyses suggested a non-neutral evolution on CYP11B2 , which suggested a modest putative signals of local adaptation. In summary, we complement the notion that effective pharmacogenetic marker(s) to predict responsiveness of anti-HT medication requires comprehensive characterization of population genetics and HT phenotypes.
Journal Article
Say cheese! Teddy Rex!
\"It's class picture day at Dino School and Teddy Rex is excited to wear his favorite sweater for the photo. But when he gets a juice stain on it, Teddy gets mad! What will he do?\"-- Provided by publisher.
Book
Mineralocorticoid Receptor and Aldosterone: Interaction Between NR3C2 Genetic Variants, Sex, and Age in a Mixed Cohort
Abstract
Context
Hypertension, a prevalent cardiovascular risk, often involves dysregulated aldosterone and its interaction with the mineralocorticoid receptor (MR). Experimental designs in animal models and human cohorts have demonstrated a sex and age dependency of aldosterone secretion that expands our pathophysiologic understanding.
Objective
This study explores the genetic variation of NR3C2, which encodes MR, in relation to aldosterone, considering age, sex, and race.
Methods
Incorporating 720 Caucasians and 145 Africans from the HyperPATH cohort, we investigated the impact of rs4835490, a single nucleotide risk allele variant, on aldosterone levels and vasculature.
Results
Notably, a significant association between rs4835490 and plasma aldosterone under liberal salt conditions emerged in individuals of European ancestry (P = .0002). Homozygous carriers of the risk A allele exhibited elevated plasma aldosterone levels (AA = 8.1 ± .9 vs GG = 4.9 ± .5 ng/dL). Additionally, aldosterone activation through posture (P = .025) and urinary excretion (P = .0122) showed notable associations. Moreover, genetic interactions with race, sex, and age were observed. Caucasian females under 50 years displayed higher plasma aldosterone, urine aldosterone, and posture aldosterone with the AA genotype compared to females over 50 years, suggesting a potential connection with menopausal or estrogen influences. Interestingly, such age-dependent interactions were absent in the African cohort.
Conclusion
Our study highlights the significance of the NR3C2 genetic variation and its interplay with age, sex, and race in aldosterone activation. The findings point toward an estrogen-modulating effect on MR activation, particularly in women, underlining the role of aldosterone dysregulation in hypertension development. This insight advances our comprehension of hypertension's complexities and opens avenues for personalized interventions.
Clinical Trial Registration Number: NCT03029806 (registered January 24, 2017).
Journal Article
Let us march on! : James Weldon Johnson and the silent protest parade
A moving and inspiring nonfiction picture book about James Weldon Johnson and the first mass all-Black march for civil rights in the United States when 10,000 Black protestors, including children, marched down New York's Fifth Avenue.
CHILDBOOK
Renin Phenotypes Characterize Vascular Disease, Autonomous Aldosteronism, and Mineralocorticoid Receptor Activity
Context:Mild cases of autonomous aldosterone secretion may go unrecognized using current diagnostic criteria for primary aldosteronism (PA).Objective:To investigate whether the inability to stimulate renin serves as a biomarker for unrecognized autonomous aldosterone secretion and mineralocorticoid receptor (MR) activation.Participants:Six hundred sixty-three normotensive and mildly hypertensive participants, who were confirmed to not have PA using current guideline criteria and were on no antihypertensive medications.Design:Participants had their maximally stimulated plasma renin activity (PRA) measured while standing upright after sodium restriction. Tertiles of maximally stimulated PRA were hypothesized to reflect the degree of MR activation: lowest PRA tertile = “Inappropriate/Excess MR Activity;” middle PRA tertile = “Intermediate MR Activity;”; and highest PRA tertile = “Physiologic MR Activity.” All participants underwent detailed biochemical and vascular characterizations under conditions of liberalized sodium intake, and associations with stimulated PRA phenotypes were performed.Results:Participants with lower stimulated PRA had greater autonomous aldosterone secretion [higher aldosterone-to-renin ratio (P = 0.002), higher urine aldosterone excretion rate (P = 0.003), higher systolic blood pressure (P = 0.004), and lower renal plasma flow (P = 0.04)] and a nonsignificant trend toward lower serum potassium and higher urine potassium excretion, which became significant after stratification by hypertension status.Conclusions:In participants without clinical PA, the inability to stimulate renin was associated with greater autonomous aldosterone secretion, impaired vascular function, and suggestive trends in potassium handling that indicate an extensive spectrum of unrecognized MR activation.In individuals without primary aldosteronism, the inability to stimulate renin is associated with unrecognized autonomous aldosterone secretion and excessive mineralocorticoid receptor activation.
Journal Article
Elevated Blood Pressure and Aldosterone Dysregulation in Young Black Women Versus White Women on Controlled Sodium Diets
Abstract
Context
Black women have a higher prevalence of hypertension as compared to White women. Differences in dietary sodium intake have been implicated as a contributing factor for the disparities in hypertension.
Objective
Our objective was to understand whether young Black women would have higher systolic blood pressure (SBP) than White women even on controlled sodium diets and to determine whether SBP differences were due to differences in dietary sodium intake and/or aldosterone regulation.
Design
The analyses included 525 hypertensive and normotensive women (ages 18-71) from the International Hypertensive Pathotype consortium, who were maintained on liberal sodium (LIB; >200 mEq sodium/day) and restricted sodium (RES; 10 mEq sodium/day) diets.
Results
Multivariate regression analyses (adjusted for age, race, study site, body mass index) found that Black women (ages 18-50) had significantly higher SBP than White women on both sodium diets: +8.7 ± 2.7 mmHg (P-value = .002) on a LIB diet and +8.5 ± 2.5 mmHg (P-value = .001) on a RES diet. Even among 18- to 35-year-olds—who were normotensive and nonobese—Black women had higher SBP: +7.9 ± 2.4 mmHg (P-value = .001) on a LIB diet and +7.6 ± 2.7 mmHg (P-value = .005) on a RES diet. Younger Black women also had higher plasma aldosterone concentration to plasma renin activity ratio (ARR) on both LIB and RES diets as well as a higher sodium-modulated aldosterone suppression-stimulation index—an indicator of aldosterone dysregulation. In younger Black women—but not in White women—there was a significant association between SBP and ARR on both LIB and RES diets.
Conclusion
Young Black women had increased SBP and ARR as compared to White women on LIB and RES diets, which offers insights into the possible mechanisms for the increased hypertension and cardiovascular disease risk in an at-risk and understudied population.
Journal Article