Genetics of coronary artery calcification among African Americans, a meta-analysis.
Ontology highlight
ABSTRACT:
SUBMITTER: Wojczynski MK
PROVIDER: S-EPMC3733595 | biostudies-literature | 2013 Jul
REPOSITORIES: biostudies-literature
Publications
Genetics of coronary artery calcification among African Americans, a meta-analysis.
Wojczynski Mary K MK Li Mingyao M Bielak Lawrence F LF Kerr Kathleen F KF Reiner Alex P AP Wong Nathan D ND Yanek Lisa R LR Qu Liming L White Charles C CC Lange Leslie A LA Ferguson Jane F JF He Jing J Young Taylor T Mosley Thomas H TH Smith Jennifer A JA Kral Brian G BG Guo Xiuqing X Wong Quenna Q Ganesh Santhi K SK Heckbert Susan R SR Griswold Michael E ME O'Leary Daniel H DH Budoff Matthew M Carr J Jeffrey JJ Taylor Herman A HA Bluemke David A DA Demissie Serkalem S Hwang Shih-Jen SJ Paltoo Dina N DN Polak Joseph F JF Psaty Bruce M BM Becker Diane M DM Province Michael A MA Post Wendy S WS O'Donnell Christopher J CJ Wilson James G JG Harris Tamara B TB Kavousi Maryam M Cupples L Adrienne LA Rotter Jerome I JI Fornage Myriam M Becker Lewis C LC Peyser Patricia A PA Borecki Ingrid B IB Reilly Muredach P MP
BMC medical genetics 20130719
<h4>Background</h4>Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants.<h4>Methods</h4>We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with ~2.5 million sing ...[more]
Similar Datasets
Project description:BackgroundCoronary artery calcification (CAC) is an imaging biomarker of coronary atherosclerosis. In European Americans, genome-wide association studies (GWAS) have identified several regions associated with coronary artery disease. However, few large studies have been conducted in African Americans. The largest meta-analysis of CAC in African Americans failed to identify genome-wide significant variants despite being powered to detect effects comparable to effects identified in European Americans. Because CAC is different in prevalence and severity in African Americans and European Americans, admixture mapping is a useful approach to identify loci missed by GWAS.ResultsWe applied admixture mapping to the African American cohort of the Family Heart Study and identified one genome-wide significant region on chromosome 12 and three potential regions on chromosomes 6, 15, and 19 that are associated with CAC. Follow-up studies using previously reported GWAS meta-analysis data suggest that the regions identified on chromosome 6 and 15 contain variants that are possibly associated with CAC. The associated region on chromosome 6 contains the gene for BMP-6, which is expressed in vascular calcific lesions.ConclusionsOur results suggest that admixture mapping can be a useful hypothesis-generating tool to identify genomic regions that contribute to complex diseases in genetically admixed populations.
| S-EPMC4417236 | biostudies-literature
Project description:Coronary artery calcium (CAC) is a strong indicator of total atherosclerosis burden. Epidemiological data have shown substantial differences in CAC prevalence and severity between African Americans and whites. However, little is known about the molecular mechanisms underlying initiation and progression of CAC. Microarray gene expression profiling of peripheral blood leucocytes was performed from 119 healthy women aged 50 yr or above in the Multi-Ethnic Study of Atherosclerosis cohort; 48 women had CAC score >100 and carotid intima-media thickness (IMT) >1 mm, while 71 had CAC <10 and IMT <0.65 mm. When 17 African Americans were compared with 41 whites in the low-CAC group, 409 differentially expressed genes (false discovery rate <5%) were identified. In addition, 316 differentially expressed genes were identified between the high- and low-CAC groups. A substantial overlap between these two gene lists was observed (148 genes, P < 10(-6)). Furthermore, genes expressed lower in African Americans also tend to express lower in individuals with low CAC (correlation 0.69, P = 0.002). Ontology analysis of the 409 race-associated genes revealed significant enrichment in mobilization of calcium and immune/inflammatory response (P < 10(-9)). Of note, 25 of 30 calcium mobilization genes were involved in immune/inflammatory response (P < 10(-10)). Our data suggest a connection between immune response and vascular calcification and the result provides a potential mechanistic explanation for the lower prevalence and severity of CAC in African Americans compared with whites.
| S-EPMC3132836 | biostudies-literature
Project description:BACKGROUND:There is increasing evidence that breast arterial calcification (BAC), an incidental finding on 3-29% of mammograms, could be used to screen for coronary artery disease (CAD). We conducted a systematic review to assess the associations between BAC and CAD and its risk factors (hypertension, hypercholesterolemia, diabetes mellitus and smoking). METHODS AND FINDINGS:MEDLINE and EMBASE databases and references of relevant papers were searched up to 18 February 2020 for English language studies that evaluated the associations of BAC and CAD and its risk factors. A single reviewer extracted all data and assessed study quality with verification by another independent reviewer, if required. Across 31 studies (n = 35,583; 3 longitudinal and 28 cross-sectional studies) that examined the association of BAC and CAD, the OR was 2.61 (95% CI 2.12-3.21; I2 = 71%). Sub-analysis of studies that graded BAC severity using the 4- (4 studies) or 12-point scale systems (3 studies) revealed an association with CAD and moderate-severe BAC (OR 4.83 (95%CI 1.50-15.54) and OR 2.95 (95%CI 1.49-5.84), respectively) but not mild BAC (OR 2.04 (95%CI 0.82-5.05) and OR 1.08 (95%CI 0.42-2.75), respectively). BAC was associated with hypertension (42 studies; n = 32,646; OR 1.80; 95% CI 1.47-2.21; I2 = 85%) and diabetes mellitus (51 studies; n = 53,464; OR 2.17; 95% CI 1.82-2.59; I2 = 75%) but not with hypercholesterolemia (OR 1.31; 95%CI 0.97-1.77; I2 = 67%). Smoking was inversely associated with BAC (35 studies; n = 40,002; OR 0.54; 95% CI 0.42-0.70; I2 = 83%). Studies mostly included symptomatic women. Marked heterogeneity existed and publication bias may be present. CONCLUSIONS:BAC is associated with CAD, diabetes mellitus and hypertension and inversely associated with smoking. Whether BAC could screen for CAD cannot be determined from current published data due to the lack of larger prospective studies. A consensus approach to quantifying BAC may also facilitate further translation into clinical care. PROSPERO: CRD42020141644.
| S-EPMC7386618 | biostudies-literature
Project description:Hyperuricemia coincides with coronary artery calcification (CAC) development, but the role of serum uric acid (SUA) as a risk factor for CAC remains unclear. The objective of this study was to gain an insight into the association between SUA and CAC in adults by performing a meta-analysis. MEDLINE, EMBASE, the Cochrane Library, and EBSCO (CINAHL) were searched for relevant observational studies published until 2 June 2019. Studies were included only if they reported data on CAC presence (Agatston score?>?0) or progression related to hyperuricemia in subclinical adult patients. The pooled estimates of crude and adjusted odds ratios (ORs) and 95% confidence interval (CI) were calculated to evaluate the association between CAC presence or progression and hyperuricemia. A total of 11 studies were identified involving 11?108 adults. The pooled OR based on the frequency of CAC presence showed that patients in the high SUA group had 1.806-fold risk for developing CAC (95% CI: 1.491-2.186) under the minimal threshold of hyperuricemia (more than 6 mg/dL or 357??moL/L). When SUA levels were analyzed as categorical variables, the pooled estimate of adjusted ORs was 1.48 (95% CI: 1.23-1.79) for CAC presence. Additionally, for each increase of 1 mg/dL of SUA level, the risk of CAC progression was increased by 31% (95% CI: 1.15-1.49) with an average follow-up duration ranged from 4.6 to 6.1?years. Hyperuricemia is closely associated with increased risk of CAC development and CAC progression in asymptomatic patients.
| S-EPMC6837029 | biostudies-literature
Project description:BackgroundThe present study aimed to evaluate the association between presence and severity of obstructive sleep apnoea (OSA) and the presence of subclinical coronary artery disease (CAD) as assessed by coronary calcium score.MethodsMedline, Cochrane, and Google Scholar databases were searched. The presence of coronary artery calcification (CAC) and CAC score were assessed.ResultsIrrespective of the cut-off value of apnoea-hypopnea index (AHI) (5 or 15 events/h), patients in the OSA group had higher rate of CAC presence and mean CAC score than those in the control group. Subgroup analyses of patients monitored with home sleep apnoea testing (HSAT) or in-hospital/laboratory polysomnography showed that the OSA group had higher rate of CAC presence and mean CAC score than the control group, except in the comparison of mean CAC score between AHI ≥5 vs. <5 events/h for patients using HSAT, which was not significant. Pair-wise comparison showed that CAC score may increase with increased OSA severity.ConclusionsIn participants without symptomatic coronary disease, the presence of OSA was associated with the presence and extent of CAC. However, potential confounders such as age, gender, and BMI and the diversity of CAC scores may affect the association.
| S-EPMC7877988 | biostudies-literature
Project description:African Americans have a 2- to 4-fold greater incidence of end-stage kidney disease (ESKD) than whites, which has long raised the possibility of a genetic cause for this disparity. Recent advances in genetic studies have shown a causal association of polymorphisms at the apolipoprotein L1 gene (APOL1) with the markedly increased risk for the nondiabetic component of the overall disparity in ESKD in African Americans. Although APOL1-associated kidney disease is thought to account for a substantial proportion of ESKD in African Americans, not all the increased risk for ESKD is accounted for, and a complete cataloging of disparities in genetic causes of ESKD eludes our current understanding of genetic-associated kidney disease. Genetic testing aids the screening, diagnosis, prognosis, and treatment of diseases with a genetic basis. Widespread use of genetic testing in clinical practice is limited by the small number of actionable genetic variants, limited health literacy of providers and patients, and underlying complex ethical, legal, and social issues. This perspective reviews racial and ethnic differences associated with genetic diseases and the development of ESKD in African Americans and discusses potential uncertainties associated with our current understanding of penetrance of genetically linked kidney disease and population-attributable risk percent.
| S-EPMC7373097 | biostudies-literature
Project description:BACKGROUND:The presence and severity of coronary artery calcified plaque (CAC) differs markedly between individuals of African and European descent, suggesting that admixture mapping may be informative for identifying genetic variants associated with subclinical cardiovascular disease. METHODS AND RESULTS:Admixture mapping of CAC was performed in 1040 unrelated African Americans with type 2 diabetes mellitus from the African American-Diabetes Heart Study, Multi-Ethnic Study of Atherosclerosis and Family Heart Study using the Illumina custom ancestry informative marker panel. All cohorts obtained computed tomography scanning of the coronary arteries using identical protocols. For each ancestry informative marker, the probability of inheriting 0, 1, and 2 copies of a European-derived allele was determined. Linkage analysis was performed by testing for association between each ancestry informative marker using these probabilities and CAC, accounting for global ancestry, age, sex, and study. Markers on 1p32.3 in the GLIS1 gene (rs6663966, logarithm of odds [LOD]=3.7), 1q32.1 near CHIT1 (rs7530895, LOD=3.1), 4q21.2 near PRKG2 (rs1212373, LOD=3.0), and 11q25 in the OPCML gene (rs6590705, LOD=3.4) had statistically significant LOD scores, whereas markers on 8q22.2 (rs6994682, LOD=2.7), 9p21.2 (rs439314, LOD=2.7), and 13p32.1 (rs7492028, LOD=2.8) manifested suggestive evidence of linkage. These regions were uniformly characterized by higher levels of European ancestry associating with higher levels or odds of CAC. Findings were replicated in 1350 African Americans without diabetes mellitus and 2497 diabetic European Americans from Multi-Ethnic Study of Atherosclerosis and the Diabetes Heart Study. CONCLUSIONS:Fine mapping these regions will likely identify novel genetic variants that contribute to CAC and clarify racial differences in susceptibility to subclinical cardiovascular disease.
| S-EPMC3578054 | biostudies-literature
Project description:ContextLipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is bound predominately to low-density lipoprotein and has been implicated as a risk factor for coronary artery disease (CAD).ObjectiveWe investigated the association between Lp-PLA(2) and CAD in a biethnic African-American and Caucasian population.DesignLp-PLA(2) mass, activity, and index, an integrated measure of mass and activity, and other cardiovascular risk factors were determined in 224 African-Americans and 336 Caucasians undergoing coronary angiography.Main outcome measuresWe assessed the distribution of Lp-PLA(2) levels and determined the predictive role of Lp-PLA(2) as a risk factor for CAD.ResultsLevels of Lp-PLA(2) mass and activity were higher among Caucasians compared with African-Americans (293 +/- 75 vs. 232 +/- 76 ng/ml, P < 0.001 for mass and 173 +/- 41 vs. 141 +/- 39 nmol/min/ml, P < 0.001 for activity, respectively). However, Lp-PLA(2) index was similar in the two groups (0.61 +/- 0.17 vs. 0.64 +/- 0.19, P = NS). In both ethnic groups, Lp-PLA(2) activity and index was significantly higher among subjects with CAD. African-American subjects with CAD had significantly higher Lp-PLA(2) index than corresponding Caucasian subjects (0.69 +/- 0.20 vs. 0.63 +/- 0.18, P = 0.028). In multivariate regression analyses, after adjusting for other risk factors, Lp-PLA(2) index was independently (odds ratio 6.7, P = 0.047) associated with CAD in African-Americans but not Caucasians.ConclusionsLp-PLA(2) activity and index was associated with presence of CAD among African-Americans and Caucasians undergoing coronary angiography. The findings suggest an independent impact of vascular inflammation among African-Americans as contributory to CAD risk and underscore the importance of Lp-PLA(2) as a cardiovascular risk factor.
| S-EPMC2869550 | biostudies-literature
Project description:Serum magnesium is inversely associated to coronary artery calcification (CAC) in patients with chronic kidney disease. There is little information on this association in a general healthy population.The aim of this study was to examine the cross-sectional association of serum magnesium levels with CAC.We included 1276 Mexican-mestizo subjects (50 % women), aged 30-75 years, free of symptomatic cardiovascular disease. CAC was quantified by multidetector computed tomography using the method described by Agatston. Cross-sectional associations of serum magnesium with cardiometabolic factors and subclinical atherosclerosis defined as a CAC score > 0, were examined in logistic regression models adjusted for age, sex, education, smoking status, body mass index, systolic blood pressure, physical activity, elevated abdominal visceral tissue, fasting insulin and glucose, alcohol consumption, menopausal status (women only), low (LDL-C) and high density lipoprotein cholesterol (HDL-C), triglycerides, diuretic use, type 2 diabetes mellitus (DM2), and family history of DM2.After full adjustment, subjects in the highest quartile of serum magnesium had 48 % lower odds of hypertension (p = 0.028), 69 % lower odds of DM2 (p = 0.003), and 42 % lower odds of CAC score > 0 (p = 0.016) compared to those with the lowest serum magnesium. The analyses also showed that a 0.17 mg/dL (1SD) increment in serum magnesium was independently associated with 16 % lower CAC (OR 0.84, 95 % CI 0.724-0.986).In a sample of Mexican-mestizo subjects, low serum magnesium was independently associated to higher prevalence not only of hypertension and DM2, but also to coronary artery calcification, which is a marker of atherosclerosis and a predictor of cardiovascular morbidity and mortality.
| S-EPMC4774001 | biostudies-other
Project description:OBJECTIVES:We evaluated the hypothesis that plasma levels of adiponectin and leptin are independently but oppositely associated with coronary artery calcification (CAC), a measure of subclinical atherosclerosis. In addition, we assessed which biomarkers of adiposity and insulin resistance are the strongest predictors of CAC beyond traditional risk factors, metabolic syndrome, and plasma C-reactive protein (CRP). BACKGROUND:Adipokines are fat-secreted biomolecules with pleiotropic actions that converge in diabetes and cardiovascular disease. METHODS:We examined the association of plasma adipocytokines with CAC in 860 asymptomatic, nondiabetic participants in the SIRCA (Study of Inherited Risk of Coronary Atherosclerosis). RESULTS:Plasma adiponectin and leptin levels had opposite and distinct associations with adiposity, insulin resistance, and inflammation. Plasma leptin was positively (top vs. bottom quartile) associated with higher CAC after adjustment for age, gender, traditional risk factors, and Framingham risk scores (tobit regression ratio 2.42 (95% confidence interval [CI]: 1.48 to 3.95; p = 0.002) and further adjustment for metabolic syndrome and CRP (tobit regression ratio: 2.31; 95% CI: 1.36 to 3.94; p = 0.002). In contrast, adiponectin levels were not associated with CAC. Comparative analyses suggested that levels of leptin, interleukin-6, and soluble tumor necrosis factor receptor-2, as well as the homeostasis model assessment of insulin resistance (HOMA-IR) index, predicted CAC scores, but only leptin and HOMA-IR provided value beyond risk factors, metabolic syndrome, and CRP. CONCLUSIONS:In SIRCA, although both leptin and adiponectin levels were associated with metabolic and inflammatory markers, only leptin was a significant independent predictor of CAC. Of several metabolic markers, leptin and the HOMA-IR index had the most robust, independent associations with CAC.
| S-EPMC2853595 | biostudies-literature