Ladenvall Per, Andersson Björn, Dellborg Mikael, Hansson Per-Olof, Eriksson Henry, Thelle Dag, Eriksson Peter
Department of Molecular and Clinical Medicine/Cardiology , Institute of Medicine, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden.
Department of Pediatrics , Göteborg Pediatric Growth Research Center, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden.
Open Heart. 2015 Apr 10;2(1):e000187. doi: 10.1136/openhrt-2014-000187. eCollection 2015.
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).
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.
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).
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, χ(2)=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.
These findings indicate that conduction by connexin 43 within the ventricular muscle distal to the specialised conduction system may be important for LBBB development.
束支传导阻滞（BBB）一直被视为传导系统疾病，但在缺乏连接蛋白40（表达于心房、近端传导系统）或连接蛋白43（表达于浦肯野细胞、心肌细胞）的小鼠中也会出现。
本文旨在探讨BBB是否具有遗传性，以及连接蛋白40和连接蛋白43基因座的多态性是否与BBB相关。
为评估BBB的遗传性，我们在人群队列“1913年出生男性研究”中筛选了患有BBB的男性的后代。使用来自具有极端QRS波时限表型的80岁男性的DNA样本，在连接蛋白40和43基因座中寻找多态性。在一个独立队列（INTERGENE）中评估已鉴定的多态性与BBB之间的关联。
“1913年出生男性研究”中77名患有BBB的男性有116名后代。在76名参与研究的后代中，2名儿子（6.4%）在54岁时患有BBB。在同一年龄，1913年出生的男性中有0.9%患有BBB。我们在连接蛋白40中鉴定出6个单核苷酸多态性（SNP），在连接蛋白43中鉴定出1个多态性。在INTERGENE队列中，连接蛋白43多态性与左束支传导阻滞（LBBB）相关（35例LBBB中有4例，232例无BBB中有16例，χ(2)=7.4，p=0.03），但与右束支传导阻滞（RBBB）或总体BBB无关。连接蛋白40的SNP或单倍型均与LBBB或RBBB无关。
这些发现表明连接蛋白43在特殊传导系统远端的心室肌内的传导可能对LBBB的发生发展很重要。
