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

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

Mónica R Meza-Meza  1   2 , Barbara Vizmanos  1   3 , Melissa Rivera-Escoto  1   2 , Adolfo I Ruiz-Ballesteros  1   2 , Karen Pesqueda-Cendejas  1   2 , Isela Parra-Rojas  1   4 , Margarita Montoya-Buelna  1   5 , Sonia Luquín  2 , Bertha Campos-López  1   2 , Paulina E Mora-García  1   2 , Sergio Cerpa-Cruz  6 , Ulises De la Cruz-Mosso  1   2
Affiliations

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

Mónica R Meza-Meza et al. Genes (Basel). .

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.

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Conflict of interest statement

The authors declare no conflict of interest and the funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Linkage disequilibrium between FokI, BsmI, ApaI, and TaqI variants in VDR in SLE patients and CS. D’ values: FokI:BsmI = 0.16, FokI:ApaI = 0.17, FokI:TaqI = 0.13, BsmI:ApaI = 0.93, BsmI:TaqI = 0.92, ApaI:TaqI = 0.78. Calculated with SHEsis online software. SLE: systemic lupus erythematosus; CS: control subjects.
Figure 2
Figure 2
Vitamin D metabolism variables by VDR genotypes and haplogenotypes in SLE patients vs. CS. (a) Calcidiol serum levels by FokI genotypes in SLE vs. CS; (b) Calcidiol serum levels by BsmI, ApaI, and TaqI haplogenotypes in SLE vs. CS; (c) Calcitriol/calcidiol ratio by FokI genotypes in SLE vs. CS; (d) Calcitriol/calcidiol ratio by BsmI, ApaI, and TaqI haplogenotypes in SLE vs. CS, I Calcitriol serum levels by FokI genotypes in SLE vs. CS; (f) Calcitriol serum levels by BsmI, ApaI, and TaqI haplogenotypes in SLE vs. CS. Data provided in medians (p05th–p95th), Mann–Whitney test. Bold numbers mean significant differences (p < 0.05). SLE: systemic lupus erythematosus.
Figure 3
Figure 3
Vitamin D metabolism variables by VDR genotypes and haplogenotypes in active vs. remission SLE patients. (a) Calcidiol serum levels by FokI genotypes in SLE by clinical activity; (b) Calcidiol serum levels by BsmI, ApaI, and TaqI haplogenotypes in SLE by clinical activity; (c) Calcitriol/calcidiol ratio by FokI genotypes in SLE by clinical activity; (d) Calcitriol/calcidiol ratio by BsmI, ApaI, and TaqI haplogenotypes in SLE by clinical activity; (e) Calcitriol serum levels by FokI genotypes in SLE by clinical activity; (f) Calcitriol serum levels by BsmI, ApaI, and TaqI haplogenotypes in SLE by clinical activity. Data provided in medians (p05th–p95th), Mann–Whitney test. Bold numbers mean significant differences (p < 0.05). SLE: systemic lupus erythematosus Clinical activity (Mex-SLEDAI ≥ 2), Remission (Mex-SLEDAI < 2).
Figure 4
Figure 4
VDR mRNA expression in SLE patients and CS. (a) VDR expression in SLE patients vs. CS (CS: reference group); (b) VDR expression in SLE patients by clinical activity (Remission: reference group); (c) VDR expression in SLE patients and CS by calcidiol categorized (Sufficiency: reference group); (d) VDR expression in SLE patients and CS by calcitriol tertiles (T1: reference grI); (e) VDR expression in SLE patients and CS by FokI genotypes (CC genotype: reference group); (f) VDR expression in SLE patients and CS by BsmI, ApaI, and TaqI haplogenotypes (GCT/GCT haplogenotype: reference group. mRNA expression. Reference group = 1. 2 −∆∆Cq Method. SLE: systemic lupus erythematosus. CS: control subjects. *: without data.
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