Background: Both schizophrenia and epilepsy have been linked to increased risk of sudden cardiac death (SCD). We hypothesized that DNA variants within genes previously associated with schizophrenia and epilepsy may contribute to an increased risk of SCD.
Objective: To investigate the contribution to SCD susceptibility of DNA variants previously implicated in schizophrenia and epilepsy.
Methods: From the ongoing Oregon Sudden Unexpected Death Study, comparisons were performed among 340 SCD cases presenting with ventricular fibrillation and 342 controls. We tested for the association between 17 single-nucleotide polymorphisms (SNPs) mapped to 14 loci previously implicated in schizophrenia and epilepsy by using logistic regression and assuming additive, dominant, and recessive genetic models.
Results: The minor allele of the nonsynonymous SNP rs10503929 within the neuregulin 1 gene was associated with SCD under all 3 investigated models, with the strongest association for the recessive genetic model (recessive P = 4.01 × 10(-5), odds ratio [OR] 4.04; additive P = 2.84 × 10(-7), OR 1.9; and dominant P = 9.01 × 10(-6), OR 2.06). To validate our findings, we further explored the association of this variant in the Harvard Cohort SCD study. The SNP rs10503929 was associated with an increased risk of SCD under the recessive genetic model (P = .0005, OR 2.7). This missense variation causes a methionine to threonine change and functional effects are currently unknown.
Conclusions: The observed association between a schizophrenia-related neuregulin 1 gene variant and SCD may represent the first evidence of coexisting genetic susceptibility between 2 conditions that have an established clinical overlap. Further investigation is warranted to explore the molecular mechanisms of this variant in the pathogenesis of SCD.
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http://dx.doi.org/10.1016/j.hrthm.2013.03.020 | DOI Listing |
Ther Adv Med Oncol
January 2025
Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada.
Non-small-cell lung cancer (NSCLC) is a highly heterogeneous disease that is frequently associated with a host of known oncogenic alterations. Advances in molecular diagnostics and drug development have facilitated the targeting of novel alterations such that the majority of NSCLC patients have driver mutations that are now clinically actionable. The goal of this review is to gain insights into clinical research and development principles by summary, analysis, and discussion of data on agents targeting known alterations in oncogene-driven, advanced NSCLC beyond those in the and the .
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Molecular Biosciences, Northwestern University; Evanston IL 60208.
The activation of progenitor cells near wound sites is a common feature of regeneration across species, but the conserved signaling mechanisms responsible for this step in whole-body regeneration are still incompletely understood. The acoel undergoes whole-body regeneration using Piwi+ pluripotent adult stem cells (neoblasts) that accumulate at amputation sites early in the regeneration process. The EGFR signaling pathway has broad roles in controlling proliferation, migration, differentiation, and cell survival across metazoans.
View Article and Find Full Text PDFCardiovasc Ther
January 2025
Department of Cardiothoracic Surgery, Ningbo Medical Center Lihuili Hospital of Ningbo University, No. 57, Xingning Rd, Ningbo City 315041, Zhejiang Province, China.
Doxorubicin (DOX) is a widely used antitumor drug; however, its use is limited by the risk of serious cardiotoxicity. Dehydroevodiamine (DHE) is a quinazoline alkaloid which has antiarrhythmic effects. The aim of this study was to investigate the protective effect of DHE on doxorubicin-induced cardiotoxicity (DIC) and its potential mechanism.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
December 2024
Center for Immunology and Cellular Biotechnology, Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia.
Background: Epidermal growth factor receptor 4 (ERBB4) and neuregulin 4 (NRG4) have been shown to reduce steatosis and prevent the development of non-alcoholic steatohepatitis in mouse models, but little to nothing is known about their role in non-alcoholic fatty liver disease (NAFLD) in humans. This study is the first to investigate the expression of and mRNAs and their role in lipid metabolism in the livers of individuals with obesity, type 2 diabetes and biopsy-proven NAFLD.
Methods: Liver biospecimens were obtained intraoperatively from 80 individuals.
Mol Med
December 2024
Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.
Background: ADAM19 (ADAM Metallopeptidase Domain 19) is known to be involved in extracellular matrix (ECM) remodeling, yet its specific function in systemic sclerosis (SSc) fibrosis remains unclear.
Objectives: This study sought to clarify the role and underlying mechanism of ADAM19 in SSc skin fibrosis.
Methods: The expression of ADAM19 was assessed in skin tissues of SSc and wound healing using publicly available transcriptome datasets.
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