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  • Genetic variation at the human connexin 43 locus but not at the connexin 40 locus is associated with left bundle branch block

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Basic and translational research
Original research article
Genetic variation at the human connexin 43 locus but not at the connexin 40 locus is associated with left bundle branch block
  1. Per Ladenvall1,
  2. Björn Andersson2,
  3. Mikael Dellborg1,
  4. Per-Olof Hansson1,
  5. Henry Eriksson1,
  6. Dag Thelle3 and
  7. Peter Eriksson1
  1. 1Department of Molecular and Clinical Medicine/Cardiology, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
  2. 2Department of Pediatrics, Göteborg Pediatric Growth Research Center, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
  3. 3Department of Community Medicine and Public Health, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
  1. Correspondence to Dr Per Ladenvall; per.ladenvall{at}gu.se

Abstract

Background Bundle branch block (BBB) has been regarded as a disease of the conduction system, but occurs in mice lacking connexin 40 (expressed in atria, proximal conduction system) or connexin 43 (expressed in Purkinje cells, cardiomyocytes).

Objective The aim of this paper is to explore whether BBB is heritable, and whether polymorphisms at connexin 40 and connexin 43 loci are associated with BBB.

Methods To assess BBB heritability, we screened descendants of men with BBB in the population cohort ‘The Study of Men Born 1913’. DNA samples from 80-year-old men with extreme QRS-duration phenotypes were used to search for polymorphisms at connexin 40 and 43 loci. Associations between identified polymorphisms and BBB were evaluated in an independent cohort (INTERGENE).

Results Seventy-seven men from ‘The Study of Men Born 1913’ with BBB had 116 descendants. Among the 76 participating descendants, 2 sons (6.4%) had BBB at 54 years of age. At the same age, 0.9% of men born in 1913 had BBB. We identified 6 single nucleotide polymorphisms (SNPs) in connexin 40 and 1 polymorphism in connexin 43. In the INTERGENE cohort, the connexin 43 polymorphism was associated with left BBB (LBBB) (4 of 35 LBBB vs 16 of 232 without BBB, χ2=7.4, p=0.03), but not with right BBB (RBBB) or overall BBB. None of the connexin 40 SNPs or haplotypes were associated with LBBB or RBBB.

Conclusions These findings indicate that conduction by connexin 43 within the ventricular muscle distal to the specialised conduction system may be important for LBBB development.

  • GENETICS

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/openhrt-2014-000187

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