Association of rs1061657 single nucleotide polymorphism of the TBX3 gene with Wolff–Parkinson–White syndrome

BACKGROUND: Wolff–Parkinson–White syndrome is one of the most well-known heart rhythm disorders characterized by pre-excitation of the ventricles. This phenomenon occurs because the electrical impulse passes through an additional conduction pathway between the atria and the ventricles. The syndrome is most commonly associated with the likelihood of supraventricular tachycardia. Numerous studies indicate the presence of a genetic component in the pathogenesis of the Wolff–Parkinson–White syndrome, which confirms its complex nature.

AIM: The study aimed to investigate the association of the rs1061657 single nucleotide polymorphism of the TBX3 gene with the Wolff–Parkinson–White syndrome.

METHODS: Patients diagnosed with the Wolff–Parkinson–White syndrome, manifesting in various clinical forms, including the Wolff–Parkinson–White phenomenon, were recruited over five years for a study based at the Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University. A total of 200 patients with the Wolff–Parkinson–White syndrome, encompassing those with the Wolff–Parkinson–White phenomenon, were examined for this paper. This group included 97 males (48.5%) and 103 females (51.5%) with a mean age of 31.9 ± 15.8 years and 38.8 ± 20.0 years, respectively. All patients underwent standard clinical, laboratory, and instrumental examinations (electrocardiography, Holter monitoring, echocardiography), as well as molecular genetic testing.

All patients were divided into the following groups by the clinical variants of the disease: 90 patients (45%) with the manifest Wolff–Parkinson–White syndrome; 60 patients (30%) with the intermittent Wolff–Parkinson–White syndrome; 46 patients (23%) with the latent Wolff–Parkinson–White syndrome; and 4 patients (2%) with the Wolff–Parkinson–White phenomenon. Excel, Statistica for Windows 10.0 (StatSoft, USA), and SPSS 20 (IBM, USA) were used for the statistical data processing.

RESULTS: A statistically significant predominance of the homozygous GG genotype was observed in the distribution of genotypes of the rs1061657 polymorphism of the TBX3 gene in patients with the Wolff–Parkinson–White syndrome compared with the control group (12.5% vs 5.5%, respectively). Furthermore, a statistically significant predominance of the G allele carriers was observed in patients with the Wolff–Parkinson–White syndrome (31.75%) compared with the control group (24.5%). The estimated risk based on odds ratio for the Wolff–Parkinson–White syndrome in the GG genotype of the TBX3 gene was 1.323-fold higher (95% confidence interval: 0.866–2.023; p = 0.04) compared with the GA and AA genotypes. In the G allele carriers, the odds ratio for the Wolff–Parkinson–White syndrome was 1.434-fold higher (95% confidence interval: 1.051–4.127; p = 0.028) compared with the A allele.

CONCLUSION: The study results confirmed that the rs1061657 polymorphism of the TBX3 gene contributes to the development of the Wolff–Parkinson–White syndrome.