TY - JOUR
T1 - Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity
AU - Freitas, Ana Teresa
AU - Calhau, Conceição
AU - Antunes, Gonçalo
AU - Araújo, Beatriz
AU - Bandeira, Matilde
AU - Barreira, Sofia
AU - Bazenga, Filipa
AU - Braz, Sandra
AU - Caldeira, Daniel
AU - Santos, Susana Constantino Rosa
AU - Faria, Ana
AU - Faria, Daniel
AU - Fraga, Marta
AU - Nogueira-Garcia, Beatriz
AU - Gonçalves, Lúcia
AU - Kovalchuk, Pavlo
AU - Lacerda, Luísa
AU - Lopes, Hugo
AU - Luís, Daniel
AU - Medeiros, Fábio
AU - Melo, Ana M.P.
AU - Melo-Cristino, José
AU - Miranda, Ana
AU - Pereira, Clara
AU - Pinto, Ana Teresa
AU - Pinto, João
AU - Proença, Helena
AU - Ramos, Angélica
AU - Rato, João P.R.
AU - Rocha, Filipe
AU - Rocha, Júlio César
AU - Moreira-Rosário, André
AU - Vazão, Helena
AU - Volovetska, Yuliya
AU - Guimarães, João Tiago
AU - Pinto, Fausto J.
N1 - Funding Information:
We thank all the study participants, who donated blood and authorized the genetic analysis and the collection of the clinical and phenotypic personal data. This project was supported by the “Fundação para a Ciência e Tecnologia”, program “Research 4 Covid-19 Apoio especial a projetos de implementação rápida para soluções inovadoras de resposta à pandemia de COVID-19”. It was also partially supported by each institution.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e−4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases. Trial registration: NCT04370808.
AB - Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e−4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases. Trial registration: NCT04370808.
UR - http://www.scopus.com/inward/record.url?scp=85117722954&partnerID=8YFLogxK
U2 - 10.1038/s41598-021-99952-z
DO - 10.1038/s41598-021-99952-z
M3 - Article
C2 - 34675344
AN - SCOPUS:85117722954
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 20837
ER -