The interferon induced transmembrane-protein 3 (IFITM3) plays an important role in the defence against viral infection. IFITM3 gene variants have been linked to differences in expression and associated with the risk of severe influenza by some authors. More recently, these variants have been associated with the risk of COVID-19 after SARS-CoV-2 infection. We determined the effect of two common IFITM3 polymorphisms (rs34481144 ​C/T and rs12252 A/G) on the risk of hospitalization due to COVID-19 by comparing 484 patients (152 required support in thr intensive care unit, ICU) and 182 age and sex matched controls (no disease symptoms). We found significantly higher frequencies of rs34481144 ​T and rs12252 ​G carriers among the patients (OR ​= ​2.02 and OR ​= ​1.51, respectively). None of the two variants were associated with ICU-admission or death. We found a significantly higher frequency of rs34481144 CC ​+ ​rs12252 AA genotype carriers among the controls, suggesting a protective effect (p = 0.001, OR = 0.56, 95%CI = 0.40–0.80). Moreover, haplotype rs34481144 ​C - rs12252 A was significantly increased in the controls (p ​= ​0.008, OR ​= ​0.71, 95%CI ​= ​0.55–0.91).

Left ventricle non-compaction cardiomyopathy (LVNC) has gained great interest in recent years, being one of the most controversial cardiomyopathies. There are several open debates, not only about its genetic heterogeneity, or about the possibility to be an acquired cardiomyopathy, but also about its possible overdiagnosis based on imaging techniques. In order to better understand this entity, we identified 38 LVNC patients diagnosed by cardiac MRI (CMRI) or anatomopathological study that could underwent NGS-sequencing and clinical study. Anatomopathological exam was performed in eight available LVNC hearts. The genetic yield was 34.2%. Patients with negative genetic testing had better left ventricular ejection fraction (LVEF) or it showed a tendency to improve in follow-up, and a possible trigger factor for LVNC was identified in 1/3 of them. Nonetheless, cerebrovascular accidents occurred in similar proportions in both groups. We conclude that in LVNC there seem to be different ways to achieve the same final phenotype. Genetic testing has a good genetic yield and provides valuable information. LVNC without an underlying genetic cause may have a better prognosis in terms of LVEF evolution. However, anticoagulation to prevent cerebrovascular accident (CVA) should be carefully evaluated in all patients. Larger series with pathologic examination are needed to help better understand this entity.

Familial hypercholesterolemia (FH) is an underdiagnosed genetic inherited condition that may lead to premature coronary artery disease (CAD). FH has an estimated prevalence in the general population of about 1:313. However, its prevalence in patients with premature STEMI (ST-elevation myocardial infarction) has not been widely studied. This study aimed to evaluate the prevalence of FH in patients with premature STEMI. Cardiovascular risk factors, LDLc (low-density lipoprotein cholesterol) evolution, and differences between genders were also evaluated. Consecutive patients were referred for cardiac catheterization to our center due to STEMI suspicion in 2018. From the 80 patients with confirmed premature CAD (men < 55 and women < 60 years old with confirmed CAD), 56 (48 men and eight women) accepted to be NGS sequenced for the main FH genes. Clinical information and DLCN (Dutch Lipid Clinic Network) score were analyzed. Only one male patient had probable FH (6–7 points) and no one reached a clinically definite diagnosis. Genetic testing confirmed that the only patient with a DLCN score ≥6 has HF (1.8%). Smoking and high BMI the most frequent cardiovascular risk factors (>80%). Despite high doses of statins being expected to reduce LDLc levels at STEMI to current dyslipidemia guidelines LDL targets (<55 mg/dL), LDLc control levels were out of range. Although still 5.4 times higher than in general population, the prevalence of FH in premature CAD is still low (1.8%). To improve the genetic yield, genetic screening may be considered among patients with probable or definite FH according to clinical criteria. The classical cardiovascular risk factors prevalence far exceeds FH prevalence in patients with premature STEMI. LDLc control levels after STEMI were out range, despite intensive hypolipemiant treatment. These findings reinforce the need for more aggressive preventive strategies in the young and for intensive lipid-lowering therapy in secondary prevention.

Mitochondrial DNA (mtDNA) differs from the nuclear genome in many aspects: a maternal inheritance pattern; being more prone to acquire somatic de novo mutations, accumulative with age; and the possible coexistence of different mtDNA alleles (heteroplasmy). Mitochondria are key cellular organelles responsible for energy production and involved in complex mechanisms, including atherosclerosis. In this scenario, we aimed to evaluate mtDNA variants that could be associated with premature cardiovascular disease. We evaluated 188 consecutive patients presenting with premature myocardial infarction with ST elevation (STEMI) confirmed by coronary angiogram. mtDNA polymorphisms and clinical data were evaluated and compared with 271 individuals from the same population (control group). Tobacco consumption (80.85% vs. 21.21%, p < 0.01) and dyslipidemia (38.83% vs. 28.41%, p = 0.02) were significantly more frequent among STEMI patients. Moreover, C16223T mtDNA mutation and poly-C heteroplasmy were significantly more frequent among premature STEMI male patients than in controls. The OR associated C16223T mtDNA with the increased presence of cardiovascular risk factors. Our data suggest that mtDNA 16223T and heteroplasmy may be associated with unstable premature atherosclerosis disease in men. Moreover, the presence of cardiovascular risk factors (CVRFs) was associated with C16223T mtDNA, with a cumulative effect. Protective mitochondrial pathways are potential therapeutic targets. Preventing exposure to the damaging mechanisms associated with CVRFs is of utmost importance.