Vitamin D Receptor (VDR) Polymorphisms in Chronic Lymphocytic Leukaemia (CLL) Patients.

Abstract

Chronic Lymphocytic Leukaemia (CLL) is a lymphoproliferative disorder in which leukaemic B cells are arrested in the G0/G1 phase of the cell cycle, resulting in their prolonged lifespan. The clinical course of CLL is highly variable with survival ranging from a few months to decades. Thus, a good prognostic tool is needed to help predict the course of the disease. The pathogenesis of CLL is unknown but it has been associated with the “escape” of B cells from apoptosis, possibly due to overexpression of anti-apoptotic genes and downregulation of pro-apoptotic genes. The expression of these genes is influenced by alterations in chromatin structure through a change in DNA methylation (chromatin remodelling) mediated by multi-protein complexes. The Vitamin D receptor (VDR), which forms part of one such chromatin remodelling complex, has been shown to be linked to the susceptibility to and outcome of other malignancies (e.g. prostate cancer). We hypothesised that VDR polymorphisms (FokI, TaqI, BsmI and ApaI) may be linked to CLL pathogenesis and/or might be a marker of CLL progression, given the immunomodulatory actions of Vitamin D. The genotypes of 34 patients with CLL were determined by either allele-specific PCR (FokI) or PCR/restriction digestion analysis (TaqI, BsmI and ApaI). Clinical data including disease stage (Rai), other prognostic markers (e.g. lymphocyte doubling time) and therapy status were recorded. Statistical analysis including Wilcoxon, Chi-square and Spearman correlation tests were performed. Initial analysis-to-date has not shown significant difference in allelic distribution between CLL patients and a healthy control population. There was no statistically significant association between the 4 VDR polymorphisms and the clinical parameters of CLL (all p>0.05). A larger cohort of CLL patients is currently under study to determine any such potential correlation.