Absence of connexin 40 gene polymorphism, as a marker of undetected atrial fibrillation in patients with unexplained cerebral ischemic events.

Background: Atrial fibrillation (AF) is a major cause of cerebral infarction. Idiopathic AF is strongly associated with the human minor connexin 40 (Cx40) promotor polymorphism. We examined the prevalence of the minor Cx40 allele in patients with cerebral ischemia and no other cardiovascular disease (CVD), as an indication of underlying idiopathic AF.

Methods: In patients with cerebral ischemia without prior CVD (n = 225), DNA analysis of the Cx40 minor allele (-44 G-->A) was performed. Patients were divided into those with a normal electrocardiographic (ECG) findings (group A, n = 164), with ECG abnormalities (group B, n = 51) and those with normal ECG and documented episodes of AF (group C, n = 10). On the basis of echocardiography (ECHO) data availability, further subgroups were defined: normal ECG and ECHO (group D, n = 45); ECG or ECHO abnormalities (group E, n = 22); and normal ECG and ECHO and documented AF episodes (group F, n = 8). The prevalence of Cx40 promotor polymorphism was compared among all the subgroups.

Results: The average age was 58.7 years (+/-11.5) and 64.4% were men. Patients with episodes of AF and those with abnormal ECG or ECHO results (B+C or E+F) did not show a higher prevalence of the minor allele genotype (AA vs. GG) compared with the normal ECG/ECHO groups (A or D) (group A, odds ratio = 1.04, 95% confidence interval: 0.26-4.11 and group D, odds ratio = 0.38, 95% confidence interval: 0.04-3.63).

Conclusion: In patients with cerebral ischemic events, without prior CVD, a higher prevalence of the Cx40 gene polymorphism, as a marker of underlying idiopathic AF appeared to be absent.