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Search Results: 1 - 10 of 208727 matches for " Amber L. Beitelshees "
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CXCL5 polymorphisms are associated with variable blood pressure in cardiovascular disease-free adults
Beitelshees Amber L,Aquilante Christina L,Allayee Hooman,Langaee Taimour Y
Human Genomics , 2012, DOI: 10.1186/1479-7364-6-9
Abstract: Objective Leukocyte count has been associated with blood pressure, hypertension, and hypertensive complications. We hypothesized that polymorphisms in the CXCL5 gene, which encodes the neutrophilic chemokine ENA-78, are associated with blood pressure in cardiovascular disease (CVD)-free adults and that these polymorphisms are functional. Methods and results A total of 192 community-dwelling participants without CVD or risk equivalents were enrolled. Two CXCL5 polymorphisms ( 156 G > C (rs352046) and 398 G > A (rs425535)) were tested for associations with blood pressure. Allele-specific mRNA expression in leukocytes was also measured to determine whether heterozygosity was associated with allelic expression imbalance. In 156 C variant carriers, systolic blood pressure (SBP) was 7 mmHg higher than in 156 G/G wild-type homozygotes (131 ± 17 vs. 124 ± 14 mmHg; P = 0.008). Similarly, diastolic blood pressure (DBP) was 4 mmHg higher in 156 C variant carriers (78 ± 11 vs. 74 ± 11 mmHg; P = 0.013). In multivariate analysis of SBP, age, sex, body mass index, and the 156 G > C polymorphism were identified as significant variables. Age, sex, and the 156 G > C SNP were further associated with DBP, along with white blood cells. Allelic expression imbalance and significantly higher circulating ENA-78 concentrations were noted for variant carriers. Conclusion CXCL5 gene polymorphisms are functional and associated with variable blood pressure in CVD-free individuals. The role of CXCL5 as a hypertension- and CVD-susceptibility gene should be further explored.
A PPARα Promoter Variant Impairs ERR-Dependent Transactivation and Decreases Mortality after Acute Coronary Ischemia in Patients with Diabetes
Sharon Cresci,Janice M. Huss,Amber L. Beitelshees,Philip G. Jones,Matt R. Minton,Gerald W. Dorn II,Daniel P. Kelly,John A. Spertus,Howard L. McLeod
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012584
Abstract: Activation of peroxisome proliferator-activated receptor alpha (PPARα) occurs in animal models of diabetes (DM) and is implicated in pathological responses to myocardial ischemia. Using bioinformatics, we identified a single nucleotide polymorphism (SNP) in the PPARα gene promoter (PPARA ?54,642 G>A; rs135561) that altered the consensus sequence for a nuclear receptor binding site. Electrophoretic mobility shift assays showed that the domain bound two known PPARA transcriptional activators, estrogen-related receptor (ERR)-α and -γ and that PPARA G bound with greater affinity than PPARA A (>2-fold; P<0.05). Likewise, promoter-reporter analyses showed enhanced transcriptional activity for PPARA G vs. PPARA A for both ERR-α and -γ (3.1 vs.1.9-fold; P<0.05). Since PPARα activation impairs post-ischemic cardiac function in experimental models of DM, we tested whether decreased PPARA transcription in PPARA A carriers favorably impacted outcome after acute coronary ischemia in 705 patients hospitalized with acute coronary syndromes (ACS; 552 Caucasian, 106 African American). PPARA A allele frequencies were similar to non-diseased subjects. However, PPARA genotype correlated with 5-year mortality in diabetic (22.2% AA vs. 18.8% AG vs. 39.5% GG; P = 0.008), but not non-diabetic (P = 0.96) subjects (genotype by diabetes interaction P = 0.008). In the diabetic ACS subjects, PPARA A carriers had strikingly reduced all-cause mortality compared to PPARA G homozygotes, (unadjusted HR 0.44, 95% CI 0.26–0.75; P = 0.003; adjusted HR 0.48, 95% CI 0.27–0.83; P = 0.009). Consistent with previous descriptions of PPARα in experimental models and human disease, we describe a novel PPARA promoter SNP that decreases transcriptional activation of PPARA and protects against mortality in diabetic patients after ACS.
Power to identify a genetic predictor of antihypertensive drug response using different methods to measure blood pressure response
Stephen T Turner, Gary L Schwartz, Arlene B Chapman, Amber L Beitelshees, John G Gums, Rhonda M Cooper-DeHoff, Eric Boerwinkle, Julie A Johnson, Kent R Bailey
Journal of Translational Medicine , 2012, DOI: 10.1186/1479-5876-10-47
Abstract: We analyzed office, home, ambulatory daytime and nighttime BP responses in hypertensive adults randomized to atenolol (N = 242) or hydrochlorothiazide (N = 257) in the Pharmacogenomic Evaluation of Antihypertensive Responses Study. Since different measured BP responses may have different predictors, we tested the "same signal" model by using linear regression methods to determine whether known predictors of BP response depend on the method of BP measurement. We estimated signal-to-noise ratios and compared power to identify a genetic polymorphism predicting BP response measured by each method separately and by weighted averages of multiple methods.After adjustment for pretreatment BP level, known predictors of BP response including plasma renin activity, race, and sex were independent of the method of BP measurement. Signal-to-noise ratios were more than 2-fold greater for home and ambulatory daytime BP responses than for office and ambulatory nighttime BP responses and up to 11-fold greater for weighted averages of all four methods. Power to identify a genetic polymorphism predicting BP response was directly related to the signal-to-noise ratio and, therefore, greatest with the weighted averages.Since different methods of measuring BP response to antihypertensive drug therapy measure the same signal, weighted averages of the BP responses measured by multiple methods minimize measurement error and optimize power to identify genetic predictors of BP response.Although office blood pressure (BP) measurements remain the standard-of-care, averages of out-of-office measurements are more reproducible [1]. Out-of-office averages have also been reported to be more strongly correlated with subclinical target organ damage [2,3] and to better predict future cardiovascular disease events [4-6] than office measurements. Not surprisingly, BP responses to antihypertensive drug therapy are more precisely and accurately determined by out-of-office than office measurements, which are
Epithelial Neutrophil-Activating Peptide (ENA-78), Acute Coronary Syndrome Prognosis, and Modulatory Effect of Statins
Issam Zineh, Amber L. Beitelshees, Gregory J. Welder, Wei Hou, Nasser Chegini, Jun Wu, Sharon Cresci, Michael A. Province, John A. Spertus
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003117
Abstract: Endothelial inflammation with chemokine involvement contributes to acute coronary syndromes (ACS). We tested the hypothesis that variation in the chemokine gene CXCL5, which encodes epithelial neutrophil-activating peptide (ENA-78), is associated with ACS prognosis. We also investigated whether statin use, a potent modulator of inflammation, modifies CXCL5's association with outcomes and characterized the in vitro effect of atorvastatin on endothelial ENA-78 production. Using a prospective cohort of ACS patients (n = 704) the association of the CXCL5 ?156 G>C polymorphism (rs352046) with 3-year all-cause mortality was estimated with hazard ratios (HR). Models were stratified by genotype and race. To characterize the influence of statins on this association, a statin*genotype interaction was tested. To validate ENA-78 as a statin target in inflammation typical of ACS, endothelial cells (HUVECs) were treated with IL-1β and atorvastatin with subsequent quantification of CXCL5 expression and ENA-78 protein concentrations. C/C genotype was associated with a 2.7-fold increase in 3-year all-cause mortality compared to G/G+G/C (95%CI 1.19–5.87; p = 0.017). Statins significantly reduced mortality in G/G individuals only (58% relative risk reduction; p = 0.0009). In HUVECs, atorvastatin dose-dependently decreased IL-1β-stimulated ENA-78 concentrations (p<0.0001). Drug effects persisted over 48 hours (p<0.01). CXCL5 genotype is associated with outcomes after ACS with potential statin modification of this effect. Atorvastatin lowered endothelial ENA-78 production during inflammation typical of ACS. These findings implicate CXCL5/ENA-78 in ACS and the statin response.
Aromatase Gene Polymorphisms Are Associated with Survival among Patients with Cardiovascular Disease in a Sex-Specific Manner
Amber L. Beitelshees,Julie A. Johnson,Megan L. Hames,Yan Gong,Rhonda M. Cooper-DeHoff,Jun Wu,Sharon Cresci,Cynthia X. Ma,Carl J. Pepine,Michael A. Province,John A. Spertus,Howard L. McLeod
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015180
Abstract: CYP19A1 encodes aromatase, the enzyme responsible for the conversion of androgens to estrogens, and may play a role in variation in outcomes among men and women with cardiovascular disease. We sought to examine genetic variation in CYP19A1 for its potential role in sex differences in cardiovascular disease outcomes.
Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment
William R. Wikoff, Reginald F. Frye, Hongjie Zhu, Yan Gong, Stephen Boyle, Erik Churchill, Rhonda M. Cooper-Dehoff, Amber L. Beitelshees, Arlene B. Chapman, Oliver Fiehn, Julie A. Johnson, Rima Kaddurah-Daouk, Pharmacometabolomics Research Network
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057639
Abstract: Antihypertensive drugs are among the most commonly prescribed drugs for chronic disease worldwide. The response to antihypertensive drugs varies substantially between individuals and important factors such as race that contribute to this heterogeneity are poorly understood. In this study we use metabolomics, a global biochemical approach to investigate biochemical changes induced by the beta-adrenergic receptor blocker atenolol in Caucasians and African Americans. Plasma from individuals treated with atenolol was collected at baseline (untreated) and after a 9 week treatment period and analyzed using a GC-TOF metabolomics platform. The metabolomic signature of atenolol exposure included saturated (palmitic), monounsaturated (oleic, palmitoleic) and polyunsaturated (arachidonic, linoleic) free fatty acids, which decreased in Caucasians after treatment but were not different in African Americans (p<0.0005, q<0.03). Similarly, the ketone body 3-hydroxybutyrate was significantly decreased in Caucasians by 33% (p<0.0001, q<0.0001) but was unchanged in African Americans. The contribution of genetic variation in genes that encode lipases to the racial differences in atenolol-induced changes in fatty acids was examined. SNP rs9652472 in LIPC was found to be associated with the change in oleic acid in Caucasians (p<0.0005) but not African Americans, whereas the PLA2G4C SNP rs7250148 associated with oleic acid change in African Americans (p<0.0001) but not Caucasians. Together, these data indicate that atenolol-induced changes in the metabolome are dependent on race and genotype. This study represents a first step of a pharmacometabolomic approach to phenotype patients with hypertension and gain mechanistic insights into racial variability in changes that occur with atenolol treatment, which may influence response to the drug.
Effects of genetic variation in H3K79 methylation regulatory genes on clinical blood pressure and blood pressure response to hydrochlorothiazide
Julio D Duarte, Issam Zineh, Ben Burkley, Yan Gong, Taimour Y Langaee, Stephen T Turner, Arlene B Chapman, Eric Boerwinkle, John G Gums, Rhonda M Cooper-DeHoff, Amber L Beitelshees, Kent R Bailey, Roger B Fillingim, Bruce C Kone, Julie A Johnson
Journal of Translational Medicine , 2012, DOI: 10.1186/1479-5876-10-56
Abstract: We investigated associations between genetic variations in this candidate pathway and HCTZ blood pressure response in two separate hypertensive cohorts (clinicaltrials.gov NCT00246519 and NCT00005520). In a secondary, exploratory analysis, we measured associations between these same genetic variations and untreated blood pressure. Associations were measured by linear regression, with only associations with P ≤ 0.01 in one cohort and replication by P ≤ 0.05 in the other cohort considered significant.In one cohort, a polymorphism in DOT1L (rs2269879) was strongly associated with greater systolic (P = 0.0002) and diastolic (P = 0.0016) blood pressure response to hydrochlorothiazide in Caucasians. However, this association was not replicated in the other cohort. When untreated blood pressure levels were analyzed, we found directionally similar associations between a polymorphism in MLLT3 (rs12350051) and greater untreated systolic (P < 0.01 in both cohorts) and diastolic (P < 0.05 in both cohorts) blood pressure levels in both cohorts. However, when further replication was attempted in a third hypertensive cohort and in smaller, normotensive samples, significant associations were not observed.Our data suggest polymorphisms in DOT1L, MLLT3, SIRT1, and SGK1 are not likely associated with blood pressure response to HCTZ. However, a possibility exists that rs2269879 in DOT1L could be associated with HCTZ response in Caucasians. Additionally, exploratory analyses suggest rs12350051 in MLLT3 may be associated with untreated blood pressure in African-Americans. Replication efforts are needed to verify roles for these polymorphisms in human blood pressure regulation.Hydrochlorothiazide (HCTZ) is one of the most commonly prescribed antihypertensive drug in the US, with approximately 118 million prescriptions dispensed in 2010, either alone or combined with another antihypertensive [1,2]. HCTZ and other thiazide diuretics are recommended by current hypertension treatment guidelin
Diffusion limits for shortest remaining processing time queues under nonstandard spatial scaling
Amber L. Puha
Mathematics , 2014, DOI: 10.1214/14-AAP1076
Abstract: We develop a heavy traffic diffusion limit theorem under nonstandard spatial scaling for the queue length process in a single server queue employing shortest remaining processing time (SRPT). For processing time distributions with unbounded support, it has been shown that standard diffusion scaling yields an identically zero limit. We specify an alternative spatial scaling that produces a nonzero limit. Our model allows for renewal arrivals and i.i.d. processing times satisfying a rapid variation condition. We add a corrective spatial scale factor to standard diffusion scaling, and specify conditions under which the sequence of unconventionally scaled queue length processes converges in distribution to the same nonzero reflected Brownian motion to which the sequence of conventionally scaled workload processes converges. Consequently, this corrective spatial scale factor characterizes the order of magnitude difference between the queue length and workload processes of SRPT queues in heavy traffic. It is determined by the processing time distribution such that the rate at which it tends to infinity depends on the rate at which the tail of the processing time distribution tends to zero. For Weibull processing time distributions, we restate this result in a manner that makes the resulting state space collapse more apparent.
International Studies of Physical Education Using SOFIT: A Review  [PDF]
Nicole J. Smith, Thomas L. McKenzie, Amber J. Hammons
Advances in Physical Education (APE) , 2019, DOI: 10.4236/ape.2019.91005
Abstract: Objective evaluations are essential to improving physical education (PE) policy and practice, and the System for Observing Fitness Instruction Time (SOFIT) is a valid and reliable tool designed to reach this end. This review assesses peer-reviewed studies that used SOFIT to describe preK-12 PE in international schools. Methods were informed by Preferred Reporting Items for Systematic Reviews (PRISMA) and articles were located by searching nine library databases and Google Scholar. A total of 739 records were located, 567 were screened, and 29 full-text articles were scrutinized. Data extraction was conducted to evaluate the characteristics of the 29 studies and to synthesize commonly reported SOFIT variables. The studies, conducted on 5 continents, included direct observations of 2703 lessons in 348 schools taught by more than 600 teachers in 10 different countries. There was substantial variability in study characteristics, how results were reported, and in study outcomes. All studies assessed physical activity (PA) and 90% (n = 26) assessed both PA and lesson context. More than two-thirds of the studies (69%; n = 20) assessed PA, lesson context, and teacher behavior. A common goal of the reviewed studies was to describe PE using SOFIT, however, researcher modifications to the established protocol and variability in how results were reported limited data syntheses and generalizations. As SOFIT is widely endorsed for assessing PE policies and practices, researchers could improve the generalizability of their study findings by adhering to the standard SOFIT protocol and by reporting results in a consistent manner.
Optimising locational access of deprived populations to farmers’ markets at a national scale: one route to improved fruit and vegetable consumption?
Amber L. Pearson,Nick Wilson
PeerJ , 2013, DOI: 10.7717/peerj.94
Abstract: Background. Evidence suggests that improved locational access to farmers’ markets increases fruit and vegetable (FV) consumption, particularly for low-income groups. Therefore, we modelled potential alternative distributions of farmers’ markets in one country (New Zealand) to explore the potential impact for deprived populations and an indigenous population (Māori). Methods. Data were collected on current farmers’ markets (n = 48), population distributions, area deprivation, and roads. Geographic analyses were performed to optimize market locations for the most deprived populations. Results. We found that, currently, farmers’ markets provided fairly poor access for the total population: 7% within 12.5 km (15 min driving time); 5% within 5 km; and 3% within 2 km. Modelling the optimal distribution of the 48 markets substantially improved access for the most deprived groups: 9% (vs 2% currently) within 12.5 km; 5% (vs 1%) within 5 km; and 3% (vs 1%) within 2 km. Access for Māori also improved: 22% (vs 7%) within 12.5 km; 12% (vs 4%) within 5 km; and 6% (vs 2%) within 2 km. Smaller pro-equity results arose from optimising the locations of the 18 least pro-equity markets or adding 10 new markets. Conclusion. These results highlight the potential for improving farmers’ market locations to increase accessibility for groups with low FV consumption. Given that such markets are easily established and relocated, local governments could consider these results to inform decisions, including subsidies for using government land and facilities. Such results can also inform central governments planning around voucher schemes for such markets and exempting them from taxes (e.g., VAT/GST).
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