Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity

Nikola Kotur; Anita Skakic; Kristel Klaassen; Vladimir Gasic; Branka Zukic; Vesna Skodric-Trifunovic; Mihailo Stjepanovic; Zorica Zivkovic; Olivera Ostojic; Goran Stevanovic; Lidija Lavadinovic; Sonja Pavlovic; Biljana Stankovic

doi:10.3389/fnut.2021.689419

Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity

Front Nutr. 2021 Jun 4:8:689419. doi: 10.3389/fnut.2021.689419. eCollection 2021.

Authors

Nikola Kotur¹, Anita Skakic¹, Kristel Klaassen¹, Vladimir Gasic¹, Branka Zukic¹, Vesna Skodric-Trifunovic^{2

3}, Mihailo Stjepanovic^{2

3}, Zorica Zivkovic^{4

5}, Olivera Ostojic⁴, Goran Stevanovic^{3

6}, Lidija Lavadinovic⁶, Sonja Pavlovic¹, Biljana Stankovic¹

Affiliations

¹ Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
² Clinic of Pulmonology, Clinical Center of Serbia, Belgrade, Serbia.
³ Medical Faculty, University of Belgrade, Belgrade, Serbia.
⁴ Children's Hospital for Lung Diseases and Tbc, MC Dr Dragisa Misovic, Belgrade, Serbia.
⁵ Faculty of Pharmacy Novi Sad, Business Academy, Novi Sad, Serbia.
⁶ Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia, Belgrade, Serbia.

Abstract

Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05-0.9) and OR 5.9 (1.4-25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles.

Keywords: COVID-19; CYP2R1; DHCR7; nutrigenetics; population genetics.