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

Area of Science:

• Cardiovascular Genetics
• Medical Genomics
• Atherosclerosis Research

Background:

• The TOMM40 single nucleotide polymorphism (SNP) rs2075650, with allelic variation c.275-31A > G, is associated with Alzheimer disease and lipid levels.
• Limited data exists on the role of TOMM40 SNP rs2075650 in cardiovascular disorders.

Purpose of the Study:

• To evaluate mortality differences based on TOMM40 genotype in patients with advanced atherosclerosis.
• To investigate the association between TOMM40 Xg and AA alleles and cardiac conduction disorders, including pacemaker (PM) or implantable cardioverter-defibrillator (ICD) implantation.

Main Methods:

• Enrolled 276 patients with significant carotid stenosis and/or lower limb ischemia.
• Genotyped patients into Xg and AA groups, assessing electrocardiographic and echocardiographic parameters.
• Conducted a clinical follow-up for approximately 82.5 months to evaluate cardiovascular events, mortality, and device implantations.

Main Results:

• No significant difference in total mortality between Xg and AA carriers (16.3% vs. 19.4%).
• Xg carriers showed higher mortality from fatal cardiovascular events (8.2% vs. 4.4%, p=0.04) and a higher incidence of left bundle branch block (LBBB) (10.2% vs. 3.1%, p=0.027).
• Xg carriers underwent device implantation significantly earlier (mean age 65.8 years) compared to AA carriers (mean age 73.1 years, p=0.049).

Conclusions:

• TOMM40 Xg genotype in advanced atherosclerosis patients is associated with increased fatal cardiovascular events and LBBB.
• Xg carriers experience earlier pacemaker or ICD implantation compared to AA carriers.
• Further research is needed to elucidate the genomic contribution of TOMM40 SNPs to cardiovascular mortality and conduction diseases.