Ethnic, Geographic, and Genetic Differences in Arsenic Metabolism at Low Arsenic Exposure: A Preliminary Analysis in the Multi-Ethnic Study of Atherosclerosis (MESA).
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ABSTRACT:
SUBMITTER: Balakrishnan P
PROVIDER: S-EPMC6025014 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
Publications
Ethnic, Geographic, and Genetic Differences in Arsenic Metabolism at Low Arsenic Exposure: A Preliminary Analysis in the Multi-Ethnic Study of Atherosclerosis (MESA).
Balakrishnan Poojitha P Jones Miranda R MR Vaidya Dhananjay D Tellez-Plaza Maria M Post Wendy S WS Kaufman Joel D JD Bielinski Suzette J SJ Taylor Kent K Francesconi Kevin K Goessler Walter W Navas-Acien Ana A
International journal of environmental research and public health 20180605 6
We investigated the effect of candidate variants in <i>AS3MT</i> (arsenic (III) methyltransferase) with urinary arsenic metabolites and their principal components in a subset of 264 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Urinary arsenic species, including inorganic arsenic (iAs), monomethylarsonate (MMA), dimethylarsinate (DMA), and arsenobetaine (Ab), were measured using high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS) a ...[more]
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| S-EPMC4434554 | biostudies-literature
Project description:BACKGROUND AND AIMS:Subclinical atherosclerosis (sCVD), measured by coronary artery calcium (CAC) and carotid intima media thickness (CIMT) is associated with cardiovascular disease (CVD). Genome-Wide Association Studies (GWAS) of sCVD and CVD have focused primarily on Caucasian populations. We hypothesized that these associations may differ in populations from distinct genetic backgrounds. METHODS:The associations between sCVD and 66 single nucleotide polymorphisms (SNPs) from published GWAS of sCVD and CVD were tested in 8224 Multi-Ethnic Study of Atherosclerosis (MESA) and MESA Family participants [2329 Caucasians (EUA), 691 Chinese (CHN), 2482 African Americans (AFA), and 2012 Hispanic (HIS)] using an additive model adjusting for CVD risk factors, with SNP significance defined by a Bonferroni-corrected p < 7.6 × 10(-4) (0.05/66). RESULTS:In EUA there were significant associations for CAC with SNPs in 9p21 (rs1333049, P = 2 × 10(-9); rs4977574, P = 4 × 10(-9)), COL4A1 (rs9515203, P = 9 × 10(-6)), and PHACTR1 (rs9349379, P = 4 × 10(-4)). In HIS, CAC was associated with SNPs in 9p21 (rs1333049, P = 8 × 10(-5); rs4977574, P = 5 × 10(-5)), APOA5 (rs964184, P = 2 × 10(-4)), and ADAMTS7 (rs7173743, P = 4 × 10(-4)). There were no associations between CAC and 9p21 SNPs for AFA and CHN. Fine mapping of the 9p21 region revealed SNPs with robust associations with CAC in EUA and HIS but no significant associations in AFA and CHN. CONCLUSION:Our results suggest some shared genetic architecture for sCVD across ethnic groups, while also underscoring the possibility of novel variants and/or pathways in risk of CVD in ethnically diverse populations.
| S-EPMC4738145 | biostudies-literature
Project description:In the USA, ethnic disparities in atherosclerosis persist after accounting for known risk factors. Ambient air pollution is associated with increased levels of atherosclerosis and differs in the USA by race/ethnicity. We estimated the influence of ambient air pollution exposure to ethnic differences in common carotid intima-media thickness (IMT).We cross-sectionally studied 6347 Caucasian-American, African-American, Hispanic and Chinese adults across 6 US cities in 2000-2002. Annual ambient air pollution concentrations (fine particulate matter [PM2.5] and oxides of nitrogen [NOX]) were estimated at each participant's residence. IMT was assessed by ultrasound.The mean IMT was 19.4 and 37.6??m smaller for Hispanic women and men, 53.6 and 7.1??m smaller for Chinese women and men, and 23.4 and 38.7??m higher for African-American women and men compared with Caucasian-American women and men. After adjustment for PM2.5, the differences in IMT remained similar for Hispanic and African-American participants but was even more negative for Chinese participants (mean IMT difference of -58.4??m for women and -15.7??m for men) compared with Caucasian-American participants. The IMT difference in Chinese participants compared with Caucasian-American participants related to their higher PM2.5 exposures was 4.8??m (95% CI 0.2 to 10.8) for women and 8.6??m (95% CI 3.4 to 15.3) for men. NOX was not related to ethnic differences in IMT.The smaller carotid IMT levels in Chinese participants were even smaller after accounting for higher PM2.5 concentrations in Chinese participants compared with Caucasian-American participants. Air pollution was not related to IMT differences in African-American and Hispanic participants compared with Caucasian-American participants.
| S-EPMC4763882 | biostudies-literature
Project description:OBJECTIVE:P-selectin is a cellular adhesion molecule that has been shown to be crucial in development of coronary heart disease (CHD). We sought to determine the role of P-selectin on the risk of atherosclerosis in a large multi-ethnic population. METHODS:Data from the Multi-Ethnic Study of Atherosclerosis (MESA), including 1628 African, 702 Chinese, 2393 non-Hispanic white, and 1302 Hispanic Americans, were used to investigate the association of plasma P-selectin with CHD risk factors, coronary artery calcium (CAC), intima-media thickness, and CHD. Regression models were used to investigate the association between P-selectin and risk factors, Tobit model for CAC, and Cox regression for CHD events. RESULTS:Mean levels of P-selectin differed by ethnicity and were higher in men (P<0.001). For all ethnic groups, P-selectin was positively associated with measures of adiposity, blood pressure, current smoking, LDL, and triglycerides and inversely with HDL. A significant ethnic interaction was observed for the association of P-selectin and prevalent diabetes; however, P-selectin was positively associated with HbA1c in all groups. Higher P-selectin levels were associated with greater prevalence of CAC. Over 10.1 years of follow-up, there were 335 incident CHD events. There was a positive linear association between P-selectin levels and rate of incident CHD after adjustment for traditional risk factors. However, association was only significant in non-Hispanic white Americans (HR: 1.81, 95% CI 1.07 to 3.07, P=0.027). CONCLUSION:We observed ethnic heterogeneity in the association of P-selectin and risk of CHD.
| S-EPMC4397161 | biostudies-literature
Project description:To investigate the cross-sectional relationship between objectively measured sleep characteristics and multiple indices of adiposity in racially/ethnically diverse older adults within the MESA Sleep study (n = 2,146).7-day actigraphy was used to assess sleep duration, sleep efficiency, and night-to-night variability. Body mass index (BMI), waist circumference, and total body fat were modeled continuously and according to obesity cut-points. Models were adjusted for demographic, socioeconomic, and behavioral variables.Participants who slept less than 6 hours a night had significantly higher BMI, waist circumference, and body fat relative to those who slept 7-8 hours. Those who slept less than 5 hours had a 16% higher prevalence of general obesity (BMI ? 30 vs. < 25 kg/m(2)) (95% [CI]: 0.08-0.24) and a 9% higher prevalence of abdominal obesity (waist circumference: women ? 88 centimeters, men ? 102 centimeters; 95% CI: 0.03-0.16) compared to those who slept 7-8 hours. Results were similar for sleep efficiency and night-to-night sleep variability.Among an older multi-ethnic cohort, we found robust associations across multiple indices of sleep and adiposity. Targeting sleep characteristics may be of benefit in obesity interventions, but more research is needed to rule out reverse causality.
| S-EPMC4989259 | biostudies-other
Project description:NHLBI TOPMed: Multi-ethnic Study of Atherosclerosis (MESA)
| PRJNA396087 | ENA
Project description:BackgroundParticulate matter (PM) exposure may directly affect the pulmonary vasculature. Although the pulmonary vasculature is not easily measurable, differential associations for right ventricular (RV) and left ventricular (LV) mass may provide an indirect assessment of pulmonary vascular damage.ObjectivesWe tested whether long-term exposure to PM < 2.5 ?m (PM2.5) is associated with greater RV mass and RV mass/end-diastolic volume ratio relative to the LV.MethodsThe Multi-Ethnic Study of Atherosclerosis performed cardiac magnetic resonance (CMR) imaging among participants 45-84 years old without clinical cardiovascular disease in 2000-2002 in six U.S. cities. A fine-scale spatiotemporal model estimated ambient PM2.5 exposure in the year before CMR; individually weighted estimates accounted for indoor exposure to ambient PM2.5. Linear regression models were adjusted for demographics, anthropometrics, smoking status, cardiac risk factors, and LV parameters, with additional adjustment for city.ResultsThe 4,041 included participants had a mean age of 61.5 years, and 47% were never smokers. The mean ambient PM2.5 was 16.4 ?g/m3 and individually weighted PM2.5 was 11.0 ?g/m3. PM2.5 exposure was associated with greater RV mass [ambient: 0.11 g per 5 ?g/m3 (95% CI: -0.05, 0.27); individually weighted: 0.20 g per 5 ?g/m3 (95% CI: 0.04, 0.36)] and a greater RV mass/end-diastolic volume ratio conditional on LV parameters. City-adjusted results for RV mass were of greater magnitude and were statistically significant for both measures of PM2.5, whereas those for RV mass/end-diastolic volume ratio were attenuated.ConclusionsLong-term PM2.5 exposures were associated with greater RV mass and RV mass/end-diastolic volume ratio conditional on the LV; however, additional adjustment for city attenuated the RV mass/end-diastolic volume findings. These findings suggest that PM2.5 exposure may be associated with subclinical cardiopulmonary differences in this general population sample.CitationAaron CP, Chervona Y, Kawut SM, Diez Roux AV, Shen M, Bluemke DA, Van Hee VC, Kaufman JD, Barr RG. 2016. Particulate matter exposure and cardiopulmonary differences in the Multi-Ethnic Study of Atherosclerosis. Environ Health Perspect 124:1166-1173;?http://dx.doi.org/10.1289/ehp.1409451.
| S-EPMC4977039 | biostudies-literature
Project description:OBJECTIVE:To describe the methodology utilized to evaluate cognitive function in the Multi-Ethnic Study of Atherosclerosis (MESA) and to present preliminary results by age, sex, and race/ethnicity. DESIGN:Cross-sectional measurements of a prospective observational cohort. SETTING:Residents of 6 U.S. communities free of cardiovascular disease at baseline (2000-02). PARTICIPANTS:4,591 adults who completed the fifth MESA clinical examination in 2011-12; mean age 70.3 (SD: 9.5) years, 53.1% women, 40.7% non-Hispanic white, 26.4% non-Hispanic black, 21.4% Hispanic, and 11.5% Chinese. MEASUREMENTS:The cognitive battery consisted of the Cognitive Abilities Screening Instrument (version 2) to evaluate global cognition, the Digit Symbol Code for processing speed and Digit Spans Forward and Backward to assess memory. Demographic, socioeconomic, and cultural covariates were also collected for descriptive statistics and multivariate modeling. RESULTS:Associations between socioeconomic factors and cognition revealed that age, race/ethnicity, education, occupational status, household income, health insurance type, household size, place of birth, years and generation in U.S., and the presence of the ApoE4 allele were significantly associated with performance on the cognitive tests, although patterns varied by specific test, racial/ethnicity, and sociocultural factors. CONCLUSION:As many of the influencing cultural and socioeconomic factors measured here are complex, multifactorial, and may not be adequately quantified, caution has been recommended with regard to comparison and interpretation of racial/ethnic group performance differences from these cross-sectional models. These data provide a baseline for future exams and more comprehensive longitudinal analyses of the contributions of subclinical and clinical diseases to cognitive function and decline.
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Project description:<p><b>MESA</b><br/> The Multi-Ethnic Study of Atherosclerosis (MESA) is a study of the characteristics of subclinical cardiovascular disease (disease detected non-invasively before it has produced clinical signs and symptoms) and the risk factors that predict progression to clinically overt cardiovascular disease or progression of the subclinical disease. MESA researchers study a diverse, population-based sample of 6,814 asymptomatic men and women aged 45-84. Thirty-eight percent of the recruited participants are white, 28 percent African-American, 22 percent Hispanic, and 12 percent Asian, predominantly of Chinese descent.</p> <p>Participants were recruited from six field centers across the United States: Wake Forest University, Columbia University, Johns Hopkins University, University of Minnesota, Northwestern University and University of California - Los Angeles. Each participant received an extensive physical exam to determine coronary calcification, ventricular mass and function, flow-mediated endothelial vasodilation, carotid intimal-medial wall thickness and presence of echogenic lucencies in the carotid artery, lower extremity vascular insufficiency, arterial wave forms, electrocardiographic (ECG) measures, standard coronary risk factors, sociodemographic factors, lifestyle factors, and psychosocial factors. Selected repetition of subclinical disease measures and risk factors at follow-up visits allows study of the progression of disease. Blood samples have been assayed for putative biochemical risk factors and stored for case-control studies. DNA has been extracted and lymphocytes cryopreserved (for possible immortalization) for study of candidate genes and possibly, genome-wide scanning, expression, and other genetic techniques. Participants are being followed for identification and characterization of cardiovascular disease events, including acute myocardial infarction and other forms of coronary heart disease (CHD), stroke, and congestive heart failure; for cardiovascular disease interventions; and for mortality.</p> <p>In addition to the six Field Centers, MESA involves a Coordinating Center, a Central Laboratory, and Central Reading Centers for Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Ultrasound, and Electrocardiography (ECG). Protocol development, staff training, and pilot testing were performed in the first 18 months of the study. The first examination took place over two years, from July 2000 - July 2002. It was followed by four examination periods that were 17-20 months in length. Participants have been contacted every 9 to 12 months throughout the study to assess clinical morbidity and mortality.</p> <p><b>MESA Family</b><br/> The general goal of the MESA Family Study, an ancillary study to MESA funded by a grant from NHLBI, is to apply modern genetic analysis and genotyping methodologies to delineate the genetic determinants of early atherosclerosis. This is being accomplished by utilizing all the current organizational structures of the <b>Multi-Ethnic Study of Atherosclerosis (MESA)</b> and Genetic Centers at Cedars-Sinai Medical Center and University of Virginia.</p> <p>In the MESA Family Study, the goal is to locate and identify genes contributing to the genetic risk for cardiovascular disease (CVD), by looking at the early changes of atherosclerosis within families (mainly siblings). 2128 individuals from 594 families, yielding 3,026 sibpairs divided between African Americans and Hispanic-Americans, were recruited by utilizing the existing framework of MESA. MESA Family studied siblings of index subjects from the MESA study and from new sibpair families (with the same demographic characteristics) and is determining the extent of genetic contribution to the variation in coronary calcium (obtained via CT Scan) and carotid artery wall thickness (B-mode ultrasound) in the two largest non-majority U.S. populations. In a small proportion of subjects, parents of MESA index subjects participating in MESA Family were studied but only to have blood drawn for genotyping.</p> <p>The MESA Family cohort was recruited from the six MESA Field Centers. MESA Family participants underwent the same examination as MESA participants during May 2004 - May 2007. DNA was extracted and lymphocytes immortalized for study of candidate genes, genome-wide linkage scanning, and analyzed for linkage with these subclinical cardiovascular traits. While linkage analysis is the primary approach being used, an additional aspect of the MESA Family Study takes advantage of the existing MESA study population for testing a variety of candidate genes for association with the same subclinical traits. Genotyping and data analysis will occur throughout the study.</p> <p><b>MESA Air</b><br/> The general goal of the Multi-Ethnic Study of Atherosclerosis and Air Pollution ('MESA Air') is to prospectively examine the relation between an individual level assessment of long-term ambient air pollution exposures (including PM<sub>2.5</sub> and the progression of subclinical cardiovascular disease in a multi-city, multi-ethnic cohort. MESA Air will also prospectively examine the relationship between an individual level assessment of long-term ambient air pollution exposures and the incidence of cardiovascular disease, including myocardial infarction and cardiovascular death. MESA AIR is funded by a grant from the United States Environmental Protection Agency to the University of Washington and subcontracts from the UW to other participating institutions.</p> <p>MESA Air will assess if ambient air pollution is associated with changes over time in subclinical measures of atherosclerosis and plasma markers of inflammation, oxidative damage, and endothelial activation in a longitudinal data model, adjusting for age, race/ethnicity, socioeconomic status, and specific cardiovascular risk factors (such as diabetes, hypertension, smoking, and diet). The study will similarly assess if the incidence of cardiovascular events is associated with long-term exposure to ambient air pollution, using a proportional hazards model. The study includes refinement of statistical tools, and explores joint/independent effects of acute and long-term pollutant exposure in the occurrence of cardiovascular disease.</p> <p>The MESA Air study is built on the foundation of the ongoing MESA study. The parent MESA Study cohort is located in six geographic areas ('Field Centers') that capture tremendous exposure heterogeneity, comparable to or greater than the variability in locations of prior U.S. cohort studies. In addition to the six Field Centers, the study involves a Coordinating Center, a Central Laboratory, and Reading Centers for Computed Tomography (CT), ultrasound and air pollution data.</p> <p>The cohort for the MESA Air study currently includes 6226 subjects: 5479 enrolled in the parent MESA study; 257 recruited specifically for this study, and 490 recruited from the MESA Family study. The entire MESA Air cohort will be followed over a 10-year project period for the occurrence of cardiovascular disease events.</p> <p>On two occasions over the ten-year study period, 3600 subjects from the MESA Air cohort, residing in nine locales, will undergo computed tomography scanning to assess presence and extent of coronary artery calcification (CAC), and ultrasound of the carotid artery to determine intima-media thickness (IMT). We will also repeatedly assess plasma markers of inflammation, oxidative damage, and endothelial function in 720 subjects.</p> <p>MESA Air adds state-of-the-art air pollution exposure assessment information to the MESA cohort study, and introduces new subjects and outcome measures to achieve our aims. The study will assess long-term individual-level exposure to ambient air pollutants for each subject using community-scale monitoring, outdoor spatial variation, subject proximity to pollution sources, pollutants' infiltration efficiency, and personal time-activity information. The exposure models will be validated using detailed monitoring in a subset of subjects.</p> <p><b>The MESA Cohort is utilized in the following dbGaP substudies.</b> To view genotypes, analysis, expression data, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" box located on the right hand side of this top-level study page phs000209 MESA Cohort. <ul> <li><a href="./study.cgi?study_id=phs000420">phs000420</a> MESA SHARe</li> <li><a href="./study.cgi?study_id=phs000283">phs000283</a> MESA CARe</li> </ul> </p>
| phs000209.v10.p2 | EGA