Angiotensin-converting enzyme 2 (ACE2) has been recognized as the entry receptor of the novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Structural and sequence variants in ACE2 gene may affect its expression in different tissues and determine a differential response to SARS-Cov-2 infection and the COVID-19-related phenotype. The present study investigated the genetic variability of ACE2 in terms of single nucleotide variants (SNVs), copy number variations (CNVs), and expression quantitative loci (eQTLs) in a cohort of 268 individuals representative of the general Italian population. The analysis identified five SNVs (rs35803318, rs41303171, rs774469453, rs773676270, and rs2285666) in the Italian cohort. Of them, rs35803318 and rs2285666 displayed a significant different frequency distribution in the Italian population with respect to worldwide population. The eQTLs analysis located in and targeting ACE2 revealed a high distribution of eQTL variants in different brain tissues, suggesting a possible link between ACE2 genetic variability and the neurological complications in patients with COVID-19. Further research is needed to clarify the possible relationship between ACE2 expression and the susceptibility to neurological complications in patients with COVID-19. In fact, patients at higher risk of neurological involvement may need different monitoring and treatment strategies in order to prevent severe, permanent brain injury.

In the present study, we investigated the distribution of genetic variations in IL6 and IL6R genes, which may be employed as prognostic and pharmacogenetic biomarkers for COVID-19 and neurodegenerative diseases. The study was performed on 271 samples representative of the Italian general population and identified seven variants (rs140764737, rs142164099, rs2069849, rs142759801, rs190436077, rs148171375, rs13306435) in IL6 and five variants (rs2228144, rs2229237, rs2228145, rs28730735, rs143810642) within IL6R, respectively. These variants have been predicted to affect the expression and binding ability of IL6 and IL6R. Ingenuity Pathway Analysis (IPA) showed that IL6 and IL6R appeared to be implicated in several pathogenetic mechanisms associated with COVID-19 severity and mortality as well as with neurodegenerative diseases mediated by neuroinflammation. Thus, the availability of IL6-IL6R-related biomarkers for COVID-19 may be helpful to counteract harmful complications and prevent multiorgan failure. At the same time, IL6-IL6R-related biomarkers could also be useful for assessing the susceptibility and progression of neuroinflammatory disorders and undertake the most suitable treatment strategies to improve patients’ prognosis and quality of life. In conclusion, this study showed how IL6 pleiotropic activity could be exploited to meet different clinical needs and realize personalized medicine protocols for chronic, age-related and modern public health emergencies.

In the present review, the main features involved in the susceptibility and progression of neurodegenerative disorders (NDDs) have been discussed, with the purpose of highlighting their potential application for promoting the management and treatment of patients with NDDs. In particular, the impact of genetic and epigenetic factors, nutrients, and lifestyle will be presented, with particular emphasis on Alzheimer’s disease (AD) and Parkinson’s disease (PD). Metabolism, dietary habits, physical exercise and microbiota are part of a complex network that is crucial for brain function and preservation. This complex equilibrium can be disrupted by genetic, epigenetic, and environmental factors causing perturbations in central nervous system homeostasis, contributing thereby to neuroinflammation and neurodegeneration. Diet and physical activity can directly act on epigenetic modifications, which, in turn, alter the expression of specific genes involved in NDDs onset and progression. On this subject, the introduction of nutrigenomics shed light on the main molecular players involved in the modulation of health and disease status. In particular, the review presents data concerning the impact of ADH1B, CYP1A2, and MTHFR on the susceptibility and progression of NDDs (especially AD and PD) and how they may be exploited for developing precision medicine strategies for the disease treatment and management.

Background: Retinal dystrophies related to damaging variants in the cadherin-related family member 1 (CDHR1) gene are rare and phenotypically heterogeneous. Here, we report a longitudinal (three-year) structure–function evaluation of a patient with a CDHR1-related retinal dystrophy. Methods: A 14-year-old girl was evaluated between 2019 and 2022. An ophthalmological assessment, including color vision, perimetry, electroretinography, and multimodal imaging of the retina, was performed periodically every six months. Next-generation sequencing disclosed two likely pathogenic/pathogenic variants in the CDHR1 gene, in compound heterozygosity, confirmed by segregation analysis. Results: At first examination, the patient showed a cone–rod pattern retinal dystrophy. Over follow-up, there was a decline of visual acuity and perimetric sensitivity (by ≥0.3 and 0.6 log units, respectively). Visual loss was associated with a progressive increase in inner retinal thickness (by 30%). Outer retina showed no detectable changes over the follow-up. Conclusions: The results indicate that, in this patient with a CDHR1-related cone–rod dystrophy, the progression to severe visual loss was paralleled by a progressive inner retinal thickening, likely a reflection of remodeling. Inner retinal changes over time may be functionally relevant in view of the therapeutic attempts based on gene therapy or stem cells to mitigate photoreceptor loss.