Vitamin D receptor polymorphisms and 25-hydroxyvitamin D in a group of Sicilian multiple sclerosis patients

Abstract

Multiple sclerosis (MS) is an auto-immune disease whose etiology remains controversial. Both genetic and environmental factors are thought to be involved in the risk of developing the disease. The purpose of our study was to assess the association of Vitamin D receptor (VDR) polymorphisms with MS and to investigate the interaction of these polymorphisms with vitamin D levels. A total of 179 Sicilian subjects, including 104 MS patients and 75 healthy controls, were studied. The most common VDR polymorphisms (Fok-I, Bsm-I, Taq-I and Apa-I) were genotyped by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analyses in both groups and serum 25-hydroxyvitamin D [25(OH)D] levels were determined in MS patients by high-performance liquid chromatography (HPLC). The distribution of genotype and allele frequencies of the four VDR polymorphisms did not differ significantly between MS patients and healthy controls, and were unrelated to the forms and the course of MS. Low serum levels of 25(OH)D were observed in MS patients but no association was observed between VDR and 25(OH)D levels except for Fok-I. Moreover, MS patients with FF and Ff genotype had a significantly lower serum levels of 25(OH)D compared with ff carriers (P < 0.05 FF vs Ff and Ff vs ff). Our findings showed no association between VDR polymorphisms and risk of MS. Interestingly, F allele could confer a genetic predisposition to lower 25(OH)D levels.

ApaI, BsmI and TaqIVDRgene polymorphisms in association with multiple sclerosis in Slovaks

“…In accordance with our findings, the role of both ApaI and TaqI VDR gene polymorphisms in MS risk was not confirmed by Smolders et al 22 in the group of 212 Dutch MS patients and 289 controls 22 or by Agnello et al 33 in 104 Sicilian MS patients and 75 controls. 30 Similarly, there was found no association between the MS susceptibility and ApaI polymorphism in a group of 104 MS patients and 104 controls from Australia, 15 or TaqI polymorphism in 69 Greek MS patients and 81 controls 26 and in 303 MS patients and 310 controls from South Spain.…”

“…In concordance with our results, the association of BsmI polymorphism with MS risk was also confirmed by Orton et al 18 in a group of 1364 MS patients from Canada (OR = 0.84, 95% CI = 0.7-1.0, p = 0.03). 17 In spite of these findings, there are several reports that did not show any association of BsmI polymorphism with MS risk, including the study of Niksresht et al 24 in 267 Iranian MS patients and 292 healthy controls, 23 Agnello et al 33 in Sicily 30 or Sioka et al 27 in Greece. 26 Only a few studies addressed the question whether the VDR gene polymorphisms are factors that can also be related to the progression and severity of MS. 15,19 The combination of TaqI allele t (C) with ApaI allele A (T) was showed to correlate with threefold increased risk of progressive course of MS (primary progressive and secondary progressive MS) in Australians.…”

“…25 In our work, we did not identify any allele or genotype association of none of the studied VDR gene polymorphisms with the rate of MS disability progression evaluated by MSSS in the cohort of the Slovak population. Similarly, in Sicilians, Agnello et al 33 did not find any association between VDR gene polymorphisms and an MS outcome in terms of EDSS, MSSS and Annualized Relapse Rates. 15 Concordantly with our findings, also two studies in Japan showed no association of the BsmI or ApaI polymorphism with the clinical course, severity of MS or with cerebral abnormalities on MRI.…”

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

“…Several genome-wide association studies (GWAS) and gene-candidate studies have investigated the influence of the specific genetic polymorphisms of vitamin D metabolites on the 25(OH)D levels, and their susceptibility to MS; one study found [92] an association between the short variant of the VDR protein (F allele) and a genetic predisposition to lower 25(OH)D levels, but not to a higher risk of MS; in a GWAS of 4501 European patients [93], single-nucleotide polymorphisms (SNPs) of the gene encoding components of the vitamin D binding protein were associated with 25(OH)D concentrations, or with the genes involved in vitamin D synthesis or activation; moreover, a genetically lowered 25(OH)D level was strongly associated with increased MS risk and progression in two studies [94,95]. …”

“…According to other authors, as a goal, the general aim is 25(OH)D levels between 40 and 60 ng/mL, and most patients should take a dose that arises from 2000 to 5000 IU/day vitamin D3 [123]. Many studies have been conducted to show the potential relationships between genome-wide association studies (GWAS) and gene-candidate studies, in order to find out the specific genetic polymorphisms of the vitamin D metabolites on the 25(OH)D levels, and their susceptibility to MS and to vitamin D supplementation efficacy in MS [92,93,94,95]. Moreover, the Human Leukocyte Antigen (HLA) haplotype might influence epistasis, trans and cis effects, and parent-of-origin effects, as well as the Epstein Barr Virus (EBV) and vitamin D effects on the course of MS [124].…”