Balkan Journal of Medical Genetics

PROGNOSTIC VALUE OF CYP1A2 (rs2069514 AND rs762551) POLYMORPHISMS IN COVID-19 PATIENTS
Bozkurt I, Gözler T, Yüksel I, Ulucan K, Tarhan KN
*Corresponding Author: Prof.Dr. Korkut Ulucan, Saray, Site Yolu Cd No:27, Umraniye/ Istanbul, Turkey, 34768, email: korkutulucan@hotmail.com.tr; +902164002222
page: 35

INTRODUCTION

Coronavirus Disease 2019 (COVID-19) was first reported as “pneumonia of uncertain etiology” in a group of patients in Wuhan, China, at the end of December 2019 [1]. Although the causative organism was initially identified as a new coronavirus (2019-nCoV), it was later changed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), as it was found to be genetically related to the coronavirus responsible for the 2003 SARS outbreak [2]. The infection spread from China to every continent of the world and was declared as an emerging pandemic by the WHO in March 2020 [3]. The COVID-19 epidemic is a pandemic caused by SARS-CoV-2, which becomes very difficult to manage after a certain stage and can often even result in death [4, 5]. Major clinical symptoms include gastrointestinal symptoms such as nausea, vomiting, and diarrhea, as well as upper respiratory symptoms such as sneezing, runny nose, and sore throat. In some patients, one week after the onset of the disease, respiratory symptoms mostly worsen, severe pneumonia was detected, acute respiratory distress syndrome (ARDS), respiratory failure, and multi-organ failure has also been detected [6]. It has been suggested that the factor leading to the death of the patient is an irregular inflammation that disrupts the exchange of oxygen (O2) and carbon dioxide (CO2) in general [7, 8]. Overwhelming proinflammatory cytokines damage alveolar epithelial and endothelial cells, leading to capillary permeability and pulmonary fibrinolysis, preventing O2 and CO2 exchange. Therefore, in the early stages of COVID-19, hypoxia occurs before the excessive inflammatory response occurs [9, 10]. However, the inflammatory response does not explain hypoxia in all COVID-19 patients. Some patients show minimal symptoms, referred to as “silent hypoxia,” despite low blood O2 levels [11]. Liu et al. (2020) reported that interferon (IFN) signaling triggered by SARS-CoV-2 induces excessive mucin production by lung epithelial cells, thickens the blood-air barrier, and inhibits O2 diffusion, leading to hypoxia. They also stated that mucin expression is driven by the aryl hydrocarbon receptor (AHR), which is a potential target for the treatment of hypoxia in COVID-19 patients [12]. Cytochrome P450 (CYP) is a protein superfamily formed by enzymes that function as monooxygenases and contain hemes as cofactors and is found in all mammalian cell types and prokaryotes except mature erythrocyte and skeletal muscle cells [13]. CYPs are the best-known as drug-metabolizing enzymes and are mainly expressed in the liver [14]. Drug metabolism mediated by CYP enzymes is oxygen dependent. Therefore, hypoxia is one of the most important factors modulating hepatic CYP enzyme expression and may interrupt the biotransformation of drugs metabolized in the liver. Recent experimental findings are consistent with early reports that sustained hypoxia leads to the down-regulation of CYP1A2 expression [15]. In overweight males over 60 years of age, the presence of comorbid metabolic disorders such as hypertension and diabetes are included in the development and severity of COVID-19 [16, 17, 18]. However, there is evidence that genetic variants can influence the development and course of infectious diseases [19]. Multiple polymorphisms, mostly single nucleotide polymorphisms (SNPs) like the rs2070874 of IL-4, rs5743708 of TLR-2 and rs1024611 of CCL-2 had been associated with susceptibility to viral respiratory infections [20]. Studies including the CYP1A2 gene and hypoxia-related diseases like COVID-19 are very limited. Also, studies that are trying to predict the prognosis, and manage the treatment of COVID-19 are inadequate to explain optimal care. The aim of this study was to examine the genotypephenotype relationship of the hypoxia-related CYP1A2 rs2069514 and rs762551 polymorphisms in patients with mild and severe COVID-19 infection and to determine their effectiveness as prognostic criteria in COVID-19.

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