Vitamin D Receptor (VDR) Genetic Variants: Relationship of FokI Genotypes with VDR Expression and Clinical Disease Activity in Systemic Lupus Erythematosus Patients

Genes (Basel). 2022 Nov 3;13(11):2016. doi: 10.3390/genes13112016.

Abstract

Vitamin D (VD) deficiency is more frequent in systemic lupus erythematosus (SLE) patients than in control subjects (CS); genetic variants in the VD receptor (VDR) could contribute to the clinical disease activity. This study was aimed to determine the association of the VDR variants FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) with susceptibility to the disease, VD status, VDR mRNA expression, and clinical disease activity in SLE patients. A cross-sectional study was conducted in 194 SLE and 196 CS Mexican women. Immunoassays quantified serum calcidiol and calcitriol. Genotyping was performed by allelic discrimination assays and mRNA VDR expression by qPCR. The FokI variant was not in linkage disequilibrium with BsmI, ApaI, and TaqI VDR variants. SLE patient carriers of the TT FokI genotype showed higher clinical disease activity scores. Notably, the mRNA VDR expression was higher in SLE patients vs. CS, in active vs. inactive SLE patients, and in participants of both study groups with vitamin D deficiency, higher calcitriol levels, and TT FokI genotype carriers. In conclusion, the TT FokI VDR genotype was related to high VDR expression and clinical disease activity in systemic lupus erythematosus patients.

Keywords: ApaI; BsmI; FokI; TaqI; VDR; calcidiol; calcitriol; polymorphism; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcitriol
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Lupus Erythematosus, Systemic* / genetics
  • RNA, Messenger / genetics
  • Receptors, Calcitriol* / genetics

Substances

  • Receptors, Calcitriol
  • methyl 4-azidophenylacetimidate
  • Calcitriol
  • RNA, Messenger
  • VDR protein, human

Grants and funding

This study was supported by Grant “Programa de Apoyo a la Mejora en las Condiciones de Producción de los Miembros del SNI y SNCA 2019-2022” (U.d.l.C.M. and B.V.) and, in part, by the Grant “Programa de Impulso a la Investigación (PIN) 2020” (U.d.l.C.M.) from the Universidad de Guadalajara for Ulises de la Cruz-Mosso, (U.d.l.C.M.).