Browsing by Subject "beta-blocker"

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  • Koponen, Mikael; Havulinna, Aki S.; Marjamaa, Annukka; Tuiskula, Annukka M.; Salomaa, Veikko; Laitinen-Forsblom, Päivi J.; Piippo, Kirsi; Toivonen, Lauri; Kontula, Kimmo; Viitasalo, Matti; Swan, Heikki (2018)
    Background: Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving beta-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations. Methods: A follow-up study covering a mean of 18.6 +/- 6.1 years was conducted in 867 genetically confirmed LQT1 and LQT2 patients and 654 non-carrier relatives aged 18-40 years. Cox regression models were used to evaluate the contribution of clinical and genetic risk factors to cardiac events. Results: In mutation carriers, risk factors for cardiac events before initiation of beta-blocker included LQT2 genotype (hazard ratio [HR] = 2.1, p = 0.002), female gender (HR = 3.2, p <0.001), a cardiac event before the age of 18 years (HR = 5.9, p <0.001), and QTc >= 500 ms (vs <470 ms, HR = 2.7, p = 0.001). LQT1 patients carrying the KCNQ1 D317N mutation were at higher risk (HR = 3.0-3.9, p <0.001-0.03) compared to G589D, c. 1129-2A > G and other KCNQ1 mutation carriers after adjusting for gender, QTc duration, and cardiac events before age 18. KCNH2 c. 453delC, L552S and R176W mutations associated with lower risk (HR = 0.11-0.23, p <0.001) than other KCNH2 mutations. Conclusions: LQT2 (compared to LQT1), female gender, a cardiac event before age 18, and long QT interval increased the risk of cardiac events in LQTS patients aged 18 to 40 years. The nature of the underlying mutation may be associated with risk variation in both LQT1 and LQT2. The identification of high-risk and low-risk mutations may enhance risk stratification.
  • Singh, Sonal; Warren, Helen R.; Hiltunen, Timo P.; McDonough, Caitrin W.; El Rouby, Nihal; Salvi, Erika; Wang, Zhiying; Garofalidou, Tatiana; Fyhrquist, Frej; Kontula, Kimmo K.; Glorioso, Valeria; Zaninello, Roberta; Glorioso, Nicola; Pepine, Carl J.; Munroe, Patricia B.; Turner, Stephan T.; Chapman, Arlene B.; Boerwinkle, Eric; Johnson, Julie A.; Gong, Yan; Cooper-DeHoff, Rhonda M. (2019)
    Background-There exists a wide interindividual variability in blood pressure (BP) response to beta(1)-blockers. To identify the genetic determinants of this variability, we performed a pharmacogenomic genome-wide meta-analysis of genetic variants beta(1)-influencing blocker BP response. Methods and Results-Genome-wide association analysis for systolic BP and diastolic BP response to beta(1)-blockers from 5 randomized clinical trials consisting of 1254 patients with hypertension of European ancestry were combined in meta-analysis and single nucleotide polymorphisms (SNPs) with P Conclusions-Data from randomized clinical trials of 8 European ancestry and 2 black cohorts support the assumption that BST1 containing locus on chromosome 4 is associated with beta(1)-blocker BP response. Given the previous associations of this region with BP, this is a strong candidate region for future functional studies and potential use in precision medicine approaches for BP management and risk prediction.