AUTHOR=Gallo Giovanna , Migliarino Serena , Cotugno Maria , Stanzione Rosita , Burocchi Simone , Bianchi Franca , Marchitti Simona , Autore Camillo , Volpe Massimo , Rubattu Speranza 

TITLE=Impact of a NDUFC2 Variant on the Occurrence of Acute Coronary Syndromes

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.921244

DOI=10.3389/fcvm.2022.921244

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>Among several potential mechanisms, mitochondrial dysfunction has been proposed to be involved in the pathogenesis of coronary artery disease (CAD). A mitochondrial complex I deficiency severely impairs cardiovascular health and contributes to CAD development. Previous evidence highlighted a key role of <italic>NDUFC2</italic>, a subunit of complex I, deficiency in the increased occurrence of renal and cerebrovascular damage in an animal model of hypertension, and of juvenile ischemic stroke occurrence in humans. Furthermore, a significant decrease of <italic>NDUFC2</italic> mRNA was detected in peripheral blood mononuclear cells from patients experiencing acute coronary syndrome (ACS). The T allele at <italic>NDUFC2</italic>/rs23117379 variant is known to associate with reduced gene expression and mitochondrial dysfunction.</p></sec><sec><title>Objective</title><p>In the present study we tested the impact of the T/C <italic>NDUFC2</italic>/rs23117379 variant on occurrence of ACS in a prospective cohort of CAD patients (<italic>n</italic> = 260).</p></sec><sec><title>Results</title><p>Hypertension, smoking habit, diabetes and hypercholesterolemia were present in a large proportion of patients. Non-ST-elevation myocardial infarction (NSTEMI) represented the most frequent type of ACS (44%, <italic>n</italic> = 115), followed by ST-elevation myocardial infarction (STEMI) (34%, <italic>n</italic> = 88) and unstable angina (22%, <italic>n</italic> = 57). The alleles/genotypes distribution for T/C at <italic>NDUFC2</italic>/rs23117379 revealed that the TT genotype was associated with a trend toward the development of ACS at an earlier age (TT 61 ± 12, CT 65 ± 12 and CC 66 ± 11 years; <italic>p</italic> = 0.051 after adjustment for gender, hypertension, smoking habit, diabetes and hypercholesterolemia) and with a significant predictive role for ACS recurrence (hazard ratio [HR]1.671; 95% confidence interval [CI], 1.138–2.472; <italic>p</italic> = 0.009).</p></sec><sec><title>Conclusions</title><p>Our findings are consistent with a deleterious effect of <italic>NDUFC2</italic> deficiency on acute coronary events predisposition and further support a role of the <italic>NDUFC2</italic>/rs23117379 variant as a genetic cardiovascular risk factor.</p></sec>