The role of BsmI and FokI vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D in Brazilian patients with systemic lupus erythematosus

Abstract

Vitamin D deficiency has been described in systemic lupus erythematosus (SLE). BsmI VDR (vitamin D receptor) gene polymorphism was associated with SLE in Asian patients. Studies in Brazilian populations have not been realized. A case-control study with 195 SLE patients and 201 healthy controls was conducted to investigate the influence of BsmI and FokI VDR gene polymorphisms on susceptibility to SLE. In addition, 25-hydroxyvitamin D [25(OH)D] was measured in SLE patients to evaluate possible associations with VDR polymorphic variants and clinical and laboratory expressions of disease. Genotyping was performed by RFLP-PCR. The measurement of 25(OH)D was performed by chemiluminescence. There was no statistically significant difference in genotype and allelic frequencies of BsmI and FokI polymorphisms between European-derived cases and controls. The mean serum levels of 25(OH)D were 25.51 ± 11.43 ng/ml in SLE patients. According to genotype distribution, 25(OH)D concentrations were significantly higher in patients carrying the FokI f/f genotype compared with patients carrying the F/F genotype (31.6 ± 14.1 ng/ml versus 23.0 ± 9.2 ng/ml, p = 0.004), reinforcing its role in the functional activity of VDR. This feature may be considered in future clinical and experimental studies involving vitamin D measurements. Therefore, genetic-specific definitions of ideal levels of vitamin D in SLE need to be established in future studies.

Vitamin D Receptor Gene BsmI and FokI Polymorphisms in Relation to Ovarian Cancer Risk in the Polish Population

“…This VDR isoform displayed higher transcriptional activity than the longer-type receptor (Arai et al, 1997). The role of the FokI SNP has recently been reinforced by Monticielo et al (2012). They found that vitamin D concentration was remarkably elevated in bearers of the TT (ff) genotype versus individuals having the CC (FF) genotype (Monticielo et al, 2012).…”

“…The role of the FokI SNP has recently been reinforced by Monticielo et al (2012). They found that vitamin D concentration was remarkably elevated in bearers of the TT (ff) genotype versus individuals having the CC (FF) genotype (Monticielo et al, 2012). The BsmI SNP may be associated with the different length polyadenylate sequence within the 3¢-untranslated region of the VDR gene (Uitterlinden et al, 2004).…”

“…The effects of BsmI and FokI SNPs on the VDR protein function have already been studied (Arai et al, 1997;Luo et al, 2012;Monticielo et al, 2012). The FokI SNP situated in exon 2 results in the formation of a second methionine start site that leads to the production of a shorter protein receptor (Arai et al, 1997).…”

Polymorphic variants in vitamin D signaling pathway genes and the risk of endometriosis-associated infertility

“…Furthermore, high frequency of the VDR (ATG) (f) allele was associated with a decrease in Th1 immune response (17). A previous study on the role of the FokI SNP demonstrated the presence of increased vitamin D levels in carriers of the TT (ff) genotype, as compared with carriers of the CC (FF) genotype (34). The presence of the VDR in normal endometrium and endometriotic implants has been demonstrated (35).…”

“…The function of BsmI and FokI SNPs on the biological effects of VDR have been extensively studied (18,(32)(33)(34). The BsmI polymorphism may change the length of the polyadenylate sequence in VDR transcript (18 significantly reduced the mRNA expression levels of VDR in carriers of the A (B) allele, as compared with subjects carrying the GG (bb) genotype (32).…”