Polymorphism of VDR Gene and the Sensitivity of Human Leukemia and Lymphoma Cells to Active Forms of Vitamin D

Abstract

The active forms of vitamin D3 (calcitriol and tacalcitol) coupled to the vitamin D receptor (VDR) are known to exhibit anti-cancer properties. However, not all cancer cells are sensitive to the active forms of vitamin D3 and its analogs. The study aimed to determine whether polymorphism of VDR is responsible for the sensitivity of human leukemia and lymphoma cells to calcitriol and tacalcitol. The impact of calcitriol and tacalcitol on the proliferation and morphology of nine different leukemia and lymphoma cell lines was determined. Only MV-4-11, Thp-1, and HL-60 cell lines sensitive to proliferation inhibition by calcitriol and tacalcitol showed morphology changes. Subsequently, the levels of the VDR and 1,25D3-MARRS proteins of calcitriol and tacalcitol binding receptors and the VDR receptor polymorphism in human leukemia and lymphoma cells were ascertained. Contrary to the current understanding, higher levels of VDR are not responsible for the greater sensitivity of cells to calcitriol and tacalcitol. Importantly, we first showed that sensitivity to calcitriol and tacalcitol in leukemias and lymphomas could be determined by the VDR polymorphism. The FokI polymorphism and the presence of the “bat” haplotype were observed only in the sensitive cells.

Vitamin D Receptor Gene Polymorphisms and the Risk of CIN2+ in Shanxi Population

“…Regarding the FOKI polymorphism, since the ff genotype and the f allele increase the incidence of CIN2+, the present results indicate that the f allele is a susceptibility allele affecting the occurrence of cervical lesions, in line with previous studies in the Thai population [ 21 ]. In addition, the f allele is also a susceptibility gene for T cell lymphoma [ 22 ], colorectal cancer [ 12 ], and ovarian cancer [ 23 ]. The FOKI f allele is associated with an increased risk of cervical cancer and most other cancers, possibly due to its reduced VDR activity [ 22 ].…”

“…In addition, the f allele is also a susceptibility gene for T cell lymphoma [ 22 ], colorectal cancer [ 12 ], and ovarian cancer [ 23 ]. The FOKI f allele is associated with an increased risk of cervical cancer and most other cancers, possibly due to its reduced VDR activity [ 22 ]. However, the meta-analysis of Pu et al [ 9 ] showed that the incidence of head and neck cancer in patients with ff genotype was significantly lower than that in patients with Ff+FF or FF genotype.…”

VDR Polymorphic Variants Are Related to Improvements in CRP and Disease Activity in Patients with Axial Spondyloarthritis That Undergo Anti-TNF Treatment

“…Four polymorphic variants in the VDR gene were selected for the experiment: rs2228570, rs1544410, rs7975232, and rs731236. The rs2228570 polymorphism (often called Fok I after the restriction enzyme widely used for its genotyping [ 23 ] is located in exon 1 of the VDR gene. It is a thymine (T) to cytosine (C) substitution that leads to changing methionine (Met) codon (ATG) into one that codes threonine (Thr) (ACG).…”

“…Those two are localized in a very close proximity in the VDR gene. As a consequence, usually the exact same primer sets are used for the PCR analysis of them both [ 23 , 27 ]. The rs7975232 cytosine (C) to adenine (A) substitution is localized in the intron and expected to affect mRNA stability and gene expression [ 28 ].…”

First Experimental Quantitative Charge Density Studies of Advanced Intermediate of Vitamin D Analogues

“…This heterodimer enables binding to the hormone response elements which enables vitamin D influence on the genomic pathway. Very recently, we have demonstrated that it is the polymorphism of the VDR gene and not only the level of the total VDR that is responsible for the sensitivity of human leukemia and lymphoma cells to vitamin D analogues [ 1 ]. As a result of the wide presence of VDR in most systems, i.e., immune, muscle and circulatory, active vitamins D regulate the functions of most cells.…”