{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:49:29Z","timestamp":1753890569222,"version":"3.41.2"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats: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 <jats:italic>NDUFC2<\/jats: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 <jats:italic>NDUFC2<\/jats:italic> mRNA was detected in peripheral blood mononuclear cells from patients experiencing acute coronary syndrome (ACS). The T allele at <jats:italic>NDUFC2<\/jats:italic>\/rs23117379 variant is known to associate with reduced gene expression and mitochondrial dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>In the present study we tested the impact of the T\/C <jats:italic>NDUFC2<\/jats:italic>\/rs23117379 variant on occurrence of ACS in a prospective cohort of CAD patients (<jats:italic>n<\/jats:italic> = 260).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats: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%, <jats:italic>n<\/jats:italic> = 115), followed by ST-elevation myocardial infarction (STEMI) (34%, <jats:italic>n<\/jats:italic> = 88) and unstable angina (22%, <jats:italic>n<\/jats:italic> = 57). The alleles\/genotypes distribution for T\/C at <jats:italic>NDUFC2<\/jats:italic>\/rs23117379 revealed that the TT genotype was associated with a trend toward the development of ACS at an earlier age (TT 61 \u00b1 12, CT 65 \u00b1 12 and CC 66 \u00b1 11 years; <jats:italic>p<\/jats: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\u20132.472; <jats:italic>p<\/jats:italic> = 0.009).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings are consistent with a deleterious effect of <jats:italic>NDUFC2<\/jats:italic> deficiency on acute coronary events predisposition and further support a role of the <jats:italic>NDUFC2<\/jats:italic>\/rs23117379 variant as a genetic cardiovascular risk factor.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.921244","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T09:19:46Z","timestamp":1654075186000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Impact of a NDUFC2 Variant on the Occurrence of Acute Coronary 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