Genome-wide association study identifies single-nucleotide polymorphism in KCNB1 associated with left ventricular mass in humans: The HyperGEN Study

<p>Abstract</p> <p>Background</p> <p>We conducted a genome-wide association study (GWAS) and validation study for left ventricular (LV) mass in the Family Blood Pressure Program – HyperGEN population. LV mass is a sensitive predictor of cardiovascular mortality and morbidity in all genders, races, and ages. Polymorphisms of candidate genes in diverse pathways have been associated with LV mass. However, subsequent studies have often failed to replicate these associations. Genome-wide association studies have unprecedented power to identify potential genes with modest effects on left LV mass. We describe here a GWAS for LV mass in Caucasians using the Affymetrix GeneChip Human Mapping 100 k Set. Cases (N = 101) and controls (N = 101) were selected from extreme tails of the LV mass index distribution from 906 individuals in the HyperGEN study. Eleven of 12 promising (<it>Q </it>< 0.8) single-nucleotide polymorphisms (SNPs) from the genome-wide study were successfully genotyped using quantitative real time PCR in a validation study.</p> <p>Results</p> <p>Despite the relatively small sample, we identified 12 promising SNPs in the GWAS. Eleven SNPs were successfully genotyped in the validation study of 704 Caucasians and 1467 African Americans; 5 SNPs on chromosomes 5, 12, and 20 were significantly (<it>P </it>≤ 0.05) associated with LV mass after correction for multiple testing. One SNP (rs756529) is intragenic within <it>KCNB1</it>, which is dephosphorylated by calcineurin, a previously reported candidate gene for LV hypertrophy within this population.</p> <p>Conclusion</p> <p>These findings suggest <it>KCNB1 </it>may be involved in the development of LV hypertrophy in humans.</p

Diagnostic value of transoesophageal echocardiography in suspected haemodynamically significant pulmonary embolism

OBJECTIVE—To assess the value of transoesophageal echocardiography (TOE) for diagnosing suspected haemodynamically significant pulmonary embolism and signs of right ventricular overload at standard echocardiography.
METHODS—113 consecutive patients (58 male; 55 female), mean (SD) age 53.6 (13.3) years, in whom there was clinical suspicion of pulmonary embolism and right ventricular overload on transthoracic echocardiography, underwent TOE in addition to routine diagnostic procedures to identify pulmonary artery thrombi.
RESULTS—TOE revealed thrombi in 32 of 51 patients who had suspected acute pulmonary embolism and in 31 of 62 with suspected chronic pulmonary embolism. In one patient a pulmonary angiosarcoma rather than chronic pulmonary embolism was found at surgery. The diagnosis of pulmonary embolism was confirmed in 77 patients by scintigraphy, spiral computed tomography, angiography, or necropsy (reference methods). While TOE failed to provide a diagnosis of pulmonary embolism in 15 of these 77 patients, no false positive findings were reported (sensitivity 80.5%, specificity 97.2%). In 11 and 26 cases, respectively, the thrombi were confined to the left or right pulmonary artery. Bilateral thrombi were found in 25( )patients. Mobile thrombi were observed only in acute pulmonary embolism (in 19 of 32 patients). No complications of TOE were noted.
CONCLUSIONS—TOE permits visualisation of pulmonary arterial thrombi, confirming the diagnosis in the majority of patients with pulmonary embolism and right ventricular overload. This may be useful for prompt decision making in patients with haemodynamic compromise considered for thrombolysis or embolectomy.


Keywords: pulmonary embolism; transoesophageal echocardiograph