The Role of TOMM40 in Cardiovascular Mortality and Conduction Disorders: An Observational Study

• Published in: Journal of clinical medicine 2024-05, Vol.13 (11), p.3177
• Main Authors: Di Stolfo, Giuseppe, Mastroianno, Sandra, Soldato, Nicolò, Massaro, Raimondo Salvatore, De Luca, Giovanni, Seripa, Davide, Urbano, Maria, Gravina, Carolina, Greco, Antonio, Siena, Paola, Ciccone, Marco Matteo, Guaricci, Andrea Igoren, Forleo, Cinzia, Carella, Massimo, Potenza, Domenico Rosario
• Format: Article
• Language: English
• Subjects: Atherosclerosis; Blood pressure; Body mass index; Cancer; Cardiovascular disease; Cholesterol; Diabetes; Ethylenediaminetetraacetic acid; Genes; Genotype & phenotype; Glucose; Health aspects; Heart attacks; Hypertension; Ischemia; Life expectancy; Medical research; Medicine, Experimental; Metabolic disorders; Mortality; Observational studies; Pacemakers; Patients; Polymorphism; Proteins; Risk factors; Single nucleotide polymorphisms; Stroke; Triglycerides; Type 2 diabetes
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm13113177

: TOMM40 single nucleotide polymorphism (SNP) rs2075650 consists of allelic variation c.275-31A > G and it has been linked to Alzheimer disease, apolipoprotein and cholesterol levels and other risk factors. However, data on its role in cardiovascular disorders are lacking. The first aim of the study is to evaluate mortality according to TOMM40 genotype in a cohort of selected patients affected by advanced atherosclerosis. Second aim was to investigate the relationship between Xg and AA alleles and the presence of conduction disorders and implantation of defibrillator (ICD) or pacemaker (PM) in our cohort. : We enrolled 276 patients (mean age 70.16 ± 7.96 years) affected by hemodynamic significant carotid stenosis and/or ischemia of the lower limbs of II or III stadium Fontaine. We divided the population into two groups according to the genotype (Xg and AA carriers). We evaluated several electrocardiographic and echocardiographic parameters, including heart rate, rhythm, presence of right and left bundle branch block (LBBB and RBBB), PR interval, QRS duration and morphology, QTc interval, and left ventricular ejection fraction (LVEF). We clinically followed these patients for 82.53 ± 30.02 months and we evaluated the incidence of cardiovascular events, number of deaths and PM/ICD implantations. We did not find a difference in total mortality between Xg and AA carriers (16.3 % vs. 19.4%; = 0.62). However, we found a higher mortality for fatal cardiovascular events in Xg carriers (8.2% vs. 4.4%; HR = 4.53, 95% CI 1.179-17.367; = 0.04) with respect to AA carriers. We noted a higher percentage of LBBB in Xg carriers (10.2% vs. 3.1%, = 0.027), which was statistically significant. Presence of right bundle branch block (RBBB) was also higher in Xg (10.2% vs. 4.4%, = 0.10), but without reaching statistically significant difference compared to AA patients. We did not observe significant differences in heart rate, presence of sinus rhythm, number of device implantations, PR and QTc intervals, QRS duration and LVEF between the two groups. At the time of enrolment, we observed a tendency for device implant in Xg carriers at a younger age compared to AA carriers (58.50 ± 0.71 y vs. 72.14 ± 11.11 y, = 0.10). During the follow-up, we noted no statistical difference for new device implantations in Xg respect to AA carriers (8.2% vs. 3.5%; HR = 2.384, 95% CI 0.718-7.922; = 0.156). The tendency to implant Xg at a younger age compared to AA patients was confirmed during follo