Titin-Truncating Variants Increase the Risk of Cardiovascular Death in Patients With Hypertrophic Cardiomyopathy

Can J Cardiol. 2017 Oct;33(10):1292-1297. doi: 10.1016/j.cjca.2017.05.020. Epub 2017 Jun 8.

Abstract

Background: Titin-truncating variants (TTNtv) have been detected in a variety of cardiomyopathies and represent the most common cause of dilated cardiomyopathy. However, their significance in hypertrophic cardiomyopathy (HCM) is still unclear.

Methods: The titin gene (TTN) was sequenced for truncating variants in a cohort of 529 Chinese patients with HCM and 307 healthy controls. Baseline and follow-up clinical data (for 4.7 ± 3.2 years) from these patients were obtained.

Results: We identified 13 and 8 TTNtv in patients with HCM (13 of 529 [2.5%]) and controls (8 of 307 [2.6%]), respectively. The prevalence of TTNtv in patients with HCM and in healthy controls was comparable (P = 0.895). There were no significant differences in baseline characteristics between patients with and those without TTNtv. However, during follow-up, patients with TTNtv (3 of 13 [23.1%]) were more likely to experience cardiovascular death compared with those without TTNtv (39 of 516 [7.6%]) [adjusted hazard ratio, 6.88; 95% confidence interval, 2.04-23.20; P = 0.002).

Conclusions: Our study suggests that TTNtv might be a genetic modifier of HCM and confer an increased risk for cardiovascular death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / metabolism
  • Cardiomyopathy, Hypertrophic / mortality
  • China / epidemiology
  • Connectin / genetics*
  • Connectin / metabolism
  • DNA / genetics*
  • DNA Mutational Analysis
  • Databases, Genetic
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction
  • Retrospective Studies
  • Survival Rate / trends
  • Time Factors
  • Transcription, Genetic

Substances

  • Connectin
  • TTN protein, human
  • DNA