The Association of Vitamin D Receptor Polymorphisms with COVID-19 Severity

Nikolaos Tentolouris; Charoula Achilla; Ioanna A Anastasiou; Ioanna Eleftheriadou; Anastasios Tentolouris; Dimitrios Basoulis; Ourania Kosta; Alexandros Lambropoulos; Maria P Yavropoulou; Anthoula Chatzikyriakidou; Edward B Jude

doi:10.3390/nu16050727

The Association of Vitamin D Receptor Polymorphisms with COVID-19 Severity

Nutrients. 2024 Mar 2;16(5):727. doi: 10.3390/nu16050727.

Affiliations

¹ 1st Department of Propaedeutic and Internal Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece.
² Laboratory of Medical Biology-Genetics, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.
³ Department of Diabetes and Endocrinology, Tameside and Glossop Integrated Care NHS Foundation Trust, Ashton-under-Lyne OL6 9RW, UK.
⁴ Division of Diabetes, Endocrinology and Gastroenterology, The University of Manchester, Manchester M13 9PL, UK.
⁵ Faculty of Science and Engineering, Manchester Metropolitan University, Manchester M15 6BH, UK.

Abstract

Background: Association studies of vitamin D receptor (VDR) polymorphisms with COVID-19 severity have produced inconsistent results in different populations. Herein we examined VDR gene polymorphisms in a Caucasian Greek cohort of COVID-19 patients.

Methods: This was a case-control study in a tertiary university hospital in Greece including 137 COVID-19 patients with varying disease severities and 72 healthy individuals. In total 209 individuals were genotyped for the FokI (rs10735810), ApaI (rs7975232), TaqI (rs731236) and BsmI (rs1544410) single-nucleotide polymorphisms (SNP) of the VDR gene by polymerase chain reaction and restriction fragment length polymorphism analysis (PCR-RFLPs). Statistical analyses were performed to determine the association between genotype and disease severity, adjusting for various confounding factors.

Results: Genotype distribution of the studied VDR SNPs in the control group was in Hardy-Weinberg equilibrium. The TaqI variant was differentially distributed between controls and COVID-19 patients according to the additive model (p = 0.009), and the CC genotype was significantly associated with an increased risk for severe COVID-19 according to the recessive model [OR: 2.52, 95%CI:1.2-5.29, p = 0.01]. Multivariate analysis demonstrated a robust association of COVID-19 severity and TaqI polymorphism in the recessive model even after adjusting for multiple confounders, including age, sex and CRP levels [Adj.OR:3.23, 95%CI:1.17-8.86, p = 0.023]. The distribution of FokI, ApaI and BsmI genotypes was similar between COVID-19 patients and controls.

Conclusions: The CC genotype of TaqI polymorphism is significantly associated with an increased risk for severe COVID-19 independently of age, sex or degree of inflammation.

Keywords: COVID-19; Greek population; severity; vitamin D receptor polymorphisms.

MeSH terms

COVID-19*
Case-Control Studies
Genetic Predisposition to Disease
Genotype
Humans
Imidoesters*
Polymorphism, Single Nucleotide
Receptors, Calcitriol* / genetics

Substances

methyl 4-azidophenylacetimidate
Receptors, Calcitriol
Imidoesters

Grants and funding

This research was funded and supported by the Special account for research grants (S.A.R.G) of the National and Kapodistrian University of Athens, grant number 8615. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No other source of funding exists.