Genome-wide association studies implicate common genetic variations in the Fine mapping analyses included Bayesian colocalization to identify the most likely causal variant. Human induced pluripotent Show more
Genome-wide association studies implicate common genetic variations in the Fine mapping analyses included Bayesian colocalization to identify the most likely causal variant. Human induced pluripotent stem cells were genome-edited using CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein 9) to delete or modify candidate enhancer regions and generate Multitrait colocalization analyses pointed at rs11172113 as the most likely causal variant in Our findings support allele-specific Show less
Hypertrophic obstructive cardiomyopathy (HOCM) is one of the most common genetic cardiac diseases and encompasses an array of clinical presentations. Little is known about the impact of genetic backgr Show more
Hypertrophic obstructive cardiomyopathy (HOCM) is one of the most common genetic cardiac diseases and encompasses an array of clinical presentations. Little is known about the impact of genetic background on outcomes after septal myectomy (SM). The aim of this study was to evaluate the effect of specific genetic mutations on midterm outcomes in adults undergoing SM for HOCM. From 2003 to 2020, a total of 59 patients (male = 66%, mean age = 52 ± 13) underwent SM after a preoperative genetic test. Patients were divided into two groups according to their test result (positive or negative). Preoperative echocardiograms were examined to identify phenotypical characteristics of each mutation. A total of thirty-one patients (53%) had a positive genetic test. MYBPC3 was the most common mutation (15/31 patients). Four different phenotypes were identified on preoperative echocardiograms. Overall, Type 1 phenotype was the most common (37% of the cohort). Type 3 was found exclusively in patients with a positive genetic test. Following SM, none of the patients required a redo myectomy or septal ablation. At 10 years, the survival was 97 ± 3% and 100% in patients with a positive and negative genetic test (p = .33), respectively. Although our results suggest that the multiple gene mutations present with different characteristics and phenotypes, midterm results of SM appear to be good regardless of genetic mutation presence. Show less
Despite the understanding of the importance of mitogen-activated protein (MAP) kinase activation in the stimulation of growth, little is known about the role of MAP kinase regulation during contact in Show more
Despite the understanding of the importance of mitogen-activated protein (MAP) kinase activation in the stimulation of growth, little is known about the role of MAP kinase regulation during contact inhibited growth control. To investigate the role of the MAP kinase extracellular signal-regulated kinase (ERK) during the transition to a contact inhibited state, cultures of normal fibroblasts (BJ) were grown to different stages of confluency. The levels of MAP kinase phosphatase (MKP) expression and the amount of active ERK and MAP ERK kinase (MEK) in these cultures were assessed through western blot analysis and were compared to fibrosarcoma cell cultures (HT-1080), which lack contact inhibition. In normal fibroblasts, the amounts of active MEK and ERK decline at contact inhibition, concurrently with a rise in MKP-1, MKP-2, and MKP-3 protein levels. In contrast, fibrosarcoma cells appear to lack density-dependent regulation of the ERK pathway. Additionally, altering the redox environment of fibrosarcoma cells to a less reducing state, as seen during contact inhibition, results in increased MKP-1 expression. Taken together, these results suggest that the altered redox environment upon contact inhibition may contribute to the regulation of ERK inactivation by MKPs. Show less