Genetic model analysis shown that the minor allele T of GJA5rs35594137 was associated with a decreased AF risk under the recessive model (OR = 0.40; 95% CI: 0.19-0.86; p = 0.018) and the minor allele G of KCNJ2 rs8079702 was associated with an increased AF risk in the recessive model (OR = 2.31; 95% CI: 1.20-4.42; p = 0.012).
The results showed that there was significant difference in the expression of CVF-I (t=3.827, P<0.01), Cx40 (t=4.21, P<0.01), and groups of the ID that keeping the electrical transmission and atrial electrical coupling synchronization (t=15.116, P<0.001), but no significant difference was found in total IDs (t=0.611, P=0.543) between patients with AF and those with sinus rhythm.
Various genes involved in Ca<sup>2+</sup> handling or gap junction formation ( Ryr2, Jph2, Gja5), potassium channels ( Kcnh2, Kcnk3), and genes implicated in atrial fibrillation ( Tbx5) were part of this ETV1-driven gene regulatory network.
In addition, a positive correlation between the mRNA expression Cx40 and KCNA5 was observed in the atrial myocytes of patients with AF (P<0.05; r=0.42).
The findings still suggested that miR-208a-3p may be involved in human chronic AF by mediating atrial Cx40 remolding, and may represent a potential therapeutic target for AF.
In this study, the correlation between the Cx 40 polymorphism (rs35594137) and AF was investigated in patients with AF in the Xinjiang, Turpan, and Kashi regions and in controls.
Three mutant forms of connexin40 (Cx40; A96S, M163V, and G38D), the primary component of the atrial gap junction channel, are associated with atrial fibrillation and retain the ability to form functional channels.
Immunoblotting showed reductions of Cx40 protein (to 77% or 49% of control values in samples from patients with paroxysmal and chronic AF, respectively), but no significant changes of Cx43 protein levels in samples from AF patients.
Gap junctions such as Cx40, Cx43 and Cx45 were proven to participate in both automaticity and conductivity of electrical impulses in SAN and atrial tissue, which was accepted as another link between SND and AF.
A germline mutation in the GJA5 gene, which encodes Cx40, resulting in a truncated Cx40 (Q49X) was identified in a large Chinese family with lone (idiopathic) atrial fibrillation (AF).
A gain-of-hemichannel function in these two atrial fibrillation-linked Cx40 mutants may provide a novel mechanism underlying the etiology of atrial fibrillation.
Sequencing results of KCNQ1, KCNH2, SCN5A, KCNA5, KCND3, KCNE1, 2, 5, KCNJ2, SCN1-3B, NPPA, and GJA5 from 192 early-onset lone AF patients were compared with data from the National Heart, Lung, and Blood Institute Exome Variant Server consisting of 6503 persons from 18 different cohort studies.
More recently germline autosomal dominantly inherited mutations in GJA5 have been found in early onset lone AF patients in several families over generations.
Remodeling in AF seems to be similar in men and women, with a tendency for women exhibiting somewhat stronger AF-induced changes in Cx40, which is probably a secondary effect because there is nothing known about hormone sensitivity of the Cx40 promoter, and a not significant tendency for higher Cx43 and collagen I.