Abstract
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.
Highlights
The identification of biological markers of disease detectable in several biological fluids and tissues represents the key milestone for the implementation of personalized medicine protocols into the clinical practice [1,2,3,4,5]
COVID-19 is just the most recent challenge for the recent challenge for the healthcare system, which has to tackle with a growing aging population healthcare system, which has to tackle with a growing aging population and the diverse pathological and the diverse pathological conditions affecting the elderly, such as neurodegenerative disorders
IL6 consists of a four-helix bundle conformation and exerts of a four-helix bundle conformation and exerts its functions by binding the interlukin-6 receptor its functions by binding the interlukin-6 receptor (IL6R) [11]
Summary
The identification of biological markers (i.e., biomarkers) of disease detectable in several biological fluids and tissues represents the key milestone for the implementation of personalized medicine protocols into the clinical practice [1,2,3,4,5]. Neurodegenerative disorders and viral infection pathologies share several molecular disorders and viral infection pathologies share several molecular signatures which, altogether, indicate signatures which, altogether, indicate the dysfunction of the local and peripheral immune system the dysfunction of the local and peripheral immune system response as a common etiopathogenetic response as a common etiopathogenetic mechanism [8,9,10]. In this context, the availability of specific mechanism [8,9,10].
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