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

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

doi:10.3389/fcvm.2022.921244

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

Front Cardiovasc Med. 2022 May 31:9:921244. doi: 10.3389/fcvm.2022.921244. eCollection 2022.

Authors

Affiliations

¹ Cardiology Unit, Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
² Division of Cardiology, Department of Medical and Surgical Science, Magna Graecia University, Catanzaro, Italy.
³ IRCCS Neuromed, Pozzilli (IS), Italy.
⁴ Cardiology Unit, Belcolle Hospital, ASL Viterbo, Viterbo, Italy.

Abstract

Background: 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 NDUFC2, 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 NDUFC2 mRNA was detected in peripheral blood mononuclear cells from patients experiencing acute coronary syndrome (ACS). The T allele at NDUFC2/rs23117379 variant is known to associate with reduced gene expression and mitochondrial dysfunction.

Objective: In the present study we tested the impact of the T/C NDUFC2/rs23117379 variant on occurrence of ACS in a prospective cohort of CAD patients (n = 260).

Results: 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%, n = 115), followed by ST-elevation myocardial infarction (STEMI) (34%, n = 88) and unstable angina (22%, n = 57). The alleles/genotypes distribution for T/C at NDUFC2/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; p = 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; p = 0.009).

Conclusions: Our findings are consistent with a deleterious effect of NDUFC2 deficiency on acute coronary events predisposition and further support a role of the NDUFC2/rs23117379 variant as a genetic cardiovascular risk factor.

Keywords: NDUFC2; acute coronary syndrome; complex I; genetic; mitochondrial dysfunction.