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Ciccarone Center Research

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Genetics

Landmark Article

Metabolomic analysis of pressure-overloaded and infarcted mouse hearts.
By: Sansbury BE, De Martino AM, Xie Z, Brooks AC, Brainard RE, Watson LJ, DeFilippis AP, Cummins TD, Harbeson MA, Brittian KR, Prabhu SD, Bhatnagar A, Jones SP, Hill BG.
These findings reveal extensive metabolic remodeling common to both hypertrophic and failing hearts that are indicative of extracellular matrix remodeling, insulin resistance and perturbations in amino acid, and lipid and nucleotide metabolism.
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
By: Arking DE, Pulit SL, Crotti L, van der Harst P, Munroe PB, Koopmann TT, Sotoodehnia N, Rossin EJ, Morley M, Wang X, Johnson AD, Lundby A, Gudbjartsson DF, Noseworthy PA, Eijgelsheim M, Bradford Y, Tarasov KV, Dörr M, Müller-Nurasyid M, Lahtinen AM, Nolte IM, Smith AV, Bis JC, Isaacs A, Newhouse SJ, Evans DS, Post WS, et al.
This integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, long-QT syndrome, and sudden cardiac death.
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Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol.
By: Lange LA, Hu Y, Zhang H, Xue C, Schmidt EM, Tang ZZ, Bizon C, Lange EM, Smith JD... Turner O‘Donnell CJ, Post WS, et al.
This large, whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.
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Genetics and personalized medicine — a role in statin therapy?
By: Patel J, Abd T, Blumenthal RS, Nasir K, Superko HR.

The primary goal of this study was to feature the most important genes involved in lipid metabolism, clinical outcomes, and statin-induced side effects, highlighting genomewide association studies and the candidate gene approach.The primary goal of this study was to feature the most important genes involved in lipid metabolism, clinical outcomes, and statin-induced side effects, highlighting genome-wide association studies and the candidate gene approach.

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APOE modulates the correlation between triglycerides, cholesterol, and CHD through pleiotropy, and gene-by-gene interactions.
By: Maxwell TJ, Ballantyne CM, Cheverud JM, Guild CS, Ndumele CE, Boerwinkle E.
The relationship between total cholesterol and triglycerides varies by apolipoprotein E isoform genotype in African-American and European-American populations.
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No association of 9p21 with arterial elasticity and retinal microvascular findings.
By: Folsom AR, Pankow JS, Li X, Duprez DA, Jacobs DR Jr, Klein R, Klein B, Tang W, Wong TY, Cotch MF, Taylor KD, Rich SS, Hall JL, Post WS, Rotter JI.
This study does not support an association of 9p21 variation with arterial elasticity or retinal microvascular abnormalities.
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Genetic variation in PEAR1 is associated with platelet aggregation and cardiovascular outcomes.
By: Lewis JP, Ryan K, O’Connell JR, Horenstein RB, Damcott CM, Gibson Q, Pollin TI, Mitchell BD, Beitelshees AL, Pakzy R, Tanner K, Parsa A, Tantry US, Bliden KP, Post WS, Faraday N, Herzog W, Gong Y, Pepine CJ, Johnson JA, Gurbel PA, Shuldiner AR.
Common genetic variation in platelet endothelial aggregation receptor-1 may be a determinant of platelet response and cardiovascular events in patients on aspirin alone or in combination with clopidogrel.
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Genetic associations with valvular calcification and aortic stenosis.
By: Thanassoulis G, Campbell CY, Owens DS, Smith JG, Smith AV, Peloso GM, Kerr KF, Pechlivanis S, Budoff MJ, Harris TB, Malhotra R, O’Brien KD, Kamstrup PR, Nordestgaard BG, Tybjaerg-Hansen A, Allison MA, Aspelund T, Criqui MH, Heckbert SR, Hwang SJ, Liu Y, Sjogren M, van der Pals J, Kälsch H, Mühleisen TW, Nöthen MM, Cupples LA, Caslake M, Di Angelantonio E, Danesh J, Rotter JI, Sigurdsson S, Wong Q, Erbel R, Kathiresan S, Melander O, Gudnason V, O’Donnell CJ, Post WS; CHARGE Extracoronary Calcium Working Group.
Genetic variation in the lipoprotein(a) locus, mediated by lipoprotein(a) levels, is associated with aortic valve calcification across multiple ethnic groups and with incident clinical aortic stenosis.
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Genome-wide association study of cardiac structure and systolic function in African Americans: the Candidate Gene Association Resource (CARe) study.
By: Fox ER, Musani SK, Barbalic M, Lin H, Yu B, Ogunyankin KO, Smith NL, Kutlar A, Glazer NL, Post WS, et al.
In the largest genome-wide association study of cardiac structure and function to date in African-Americans, researchers identified 4 genetic loci related to left ventricular mass, interventricular septal wall thickness, left ventricular internal diastolic diameter, and ejection fraction, which reached genome-wide significance.
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The ABCG8 G574R variant, serum plant sterol levels, and cardiovascular disease risk in the Old Order Amish.
By: Horenstein RB, Mitchell BD, Post WS, Lütjohann D, von Bergmann K, Ryan KA, Terrin M, Shuldiner AR, Steinle NI.

Although the G574R variant is associated with moderately elevated plant sterol levels, carriers of the 574R allele had modestly lower levels of carotid wall thickness compared with noncarriers.

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