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Measurement of heritability of myocardial blood flow by positron emission tomography: the Twins Heart Study.

ABSTRACT: To estimate the heritability of myocardial blood flow (MBF) and coronary flow reserve (CFR) measured with positron emission tomography (PET).Cross-sectional twin study.General clinical research centre of a university hospital at Atlanta, USA.A sample of 180 middle-aged (mean±SD 55±2.9 years) male twins, including 107 monozygotic and 73 dizygotic twins.All twins underwent imaging of MBF with PET (13)NH(3) at rest and after adenosine stress during a single imaging session. Structural equation modelling was used to estimate the heritability of MBF at rest and during adenosine stress, as well as of CFR.The basal MBF (mean±SD) was 0.69±0.20 ml/min/g, and the MBF during adenosine stress was 1.70±0.49 ml/min/g; the CFR was 2.62±0.99. There was substantial heritability for MBF both at rest (0.48, 95% CI 0.29 to 0.64) and during adenosine stress (0.51, 95% CI 0.29 to 0.68), as well as CFR (0.48, 95% CI 0.26 to 0.65).For the first time, a substantial genetic contribution to the interindividual variation in MBF and CFR measured with PET in middle-aged men has been demonstrated. The data suggest that a fruitful direction for future work would be the identification of genetic variants for early atherosclerotic stages assessed by PET imaging.

SUBMITTER: Su S

PROVIDER: S-EPMC4380432 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Measurement of heritability of myocardial blood flow by positron emission tomography: the Twins Heart Study.

Su Shaoyong S Votaw John J Faber Tracy T Khan Durreshahwar D Bremner J Douglas JD Goldberg Jack J Nichols Ken K Van Tosh Andrew A Vaccarino Viola V

Heart (British Cardiac Society) 20120209 6

<h4>Objective</h4>To estimate the heritability of myocardial blood flow (MBF) and coronary flow reserve (CFR) measured with positron emission tomography (PET).<h4>Design</h4>Cross-sectional twin study.<h4>Setting</h4>General clinical research centre of a university hospital at Atlanta, USA.<h4>Patients</h4>A sample of 180 middle-aged (mean±SD 55±2.9 years) male twins, including 107 monozygotic and 73 dizygotic twins.<h4>Main outcome measures</h4>All twins underwent imaging of MBF with PET (13)NH ...[more]

PMID: 22323242

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Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

Dataset Information

Measurement of heritability of myocardial blood flow by positron emission tomography: the Twins Heart Study.

Publications

Measurement of heritability of myocardial blood flow by positron emission tomography: the Twins Heart Study.

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