Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis

Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Multiple Sclerosis (Impact Factor: 4.82). 12/2009; 16(2):133-8. DOI: 10.1177/1352458509355069
Source: PubMed


The extent to which potential genetic determinants of vitamin D levels may be related to multiple sclerosis (MS) risk has not been thoroughly explored. The objective of this study was to determine whether polymorphisms in VDR, CYP27B1, CYP24A1, CYP2R1 and DBP are associated with the risk of MS and whether these variants may modify associations between environmental or dietary vitamin D on MS risk. A nested case-control study was conducted in two, large cohorts of US nurses, including 214 MS cases and 428 age-matched controls. Conditional logistic regression models were used to calculate relative risks (RR) and 95% confidence intervals (CIs) and to assess the significance of gene-environment interactions. No associations were observed for any of the single-nucleotide polymorphisms (SNPs) in VDR, CYP27B1, CYP24A1, CYP2R1 or DBP (p > 0.05 for all). The authors did observe an interaction (p = 0.04) between dietary intake of vitamin D and the vitamin D receptor FokI polymorphism on MS risk. The protective effect of increasing vitamin D was evident only in individuals with the 'ff ' genotype (RR = 0.2, 95% CI: 0.06, 0.78; p = 0.02 for 400 IU/day increase). It was concluded that this does not support a role for the selected SNPs involved in vitamin D metabolism in the etiology of MS. The finding of a marginally significant gene-environment interaction requires replication in larger datasets, but suggests future genetic studies may benefit from considering relevant environmental context.

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    • "Simon et al. [15] reported a significant interaction between vitamin D intake and rs2228570 polymorphism (80% of decreased risk of MS for an increase of 400 IU/day of vitamin D in patients homozygous for the minor allele). Agliardi et al. [22] reported decreased MS risk for rs731236TT genotype in HLA-DRB1*15 positive individuals, and Cox et al. [19] reported a trend for increasing risk of MS in subjects who were homozygous for the HLADRB1*1501 (rs3135388) allele in association with rs2228570. "
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    ABSTRACT: Some epidemiological, genetic, and experimental data suggest a possible role of vitamin D in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis. Data on the possible contribution of several single nucleotide polymorphisms (SNP) in the vitamin D receptor (VDR) gene to the risk for MS are controversial. Several studies suggested an interaction between some SNPs in the VDR gene and HLADRB1*1501 in the risk for MS. The aim of this study was to investigate a possible influence of the SNPs rs2228570 and rs731236 in the VDR gene in the risk for MS. A secondary objective was to address the possible interactions between VDR genes and HLADRB1*1501. We analyzed the allelic and genotype frequency of VDR rs2228570, rs731236, and HLADRB1*1501 (rs3135388) in 303 patients with MS and 310 healthy controls, using TaqMan Assays. We also conducted a meta-analysis, that was carried out by using the software Meta-Disc 1.1.1 (; Unit of Clinical Statistics, Hospital Ramón y Cajal, Madrid, Spain). Heterogeneity between studies in terms of degree of association was tested using the Q-statistic. VDR rs2228570 and rs731236 allelic and genotype frequencies did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. HLADRB1*1501 showed a high association with the risk of developing MS 4.76(95% C.I. = 3.14-7.27; p<0.0001). The meta-analysis, after excluding data of one study that was responsible of heterogeneity for rs731236 polymorphism, showed lack of relation of both SNPs with the risk for MS. HLADRB1*1501 showed lack of interaction with VDR rs2228570 and rs731236 in increasing MS risk. These results suggest that VDR rs2228570 and rs731236 polymorphisms are not related with the risk for MS, and did not confirm interaction between these VDR SNPs and HLADRB1 in the risk for MS.
    PLoS ONE 06/2013; 8(6):e65487. DOI:10.1371/journal.pone.0065487 · 3.23 Impact Factor
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    • "Thus, a US study in 214 MS cases and 428 age-matched controls found no associations for any of the single-nucleotide polymorphisms in VDR, but found an interaction between dietary intake of vitamin D and the VDR Fok-I polymorphism on MS risk. Specifically, individuals with the ff genotype had decreased MS risk with higher vitamin D intake [16]. Negative results have been reported in a Canadian study employed restriction fragment length polymorphisms and highly polymorphic microsatellite markers to study VDR gene polymorphisms and MS risk [15]. "
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    ABSTRACT: Polymorphisms of the vitamin D receptor (VDR) gene have been linked to both multiple sclerosis (MS) and osteoporosis. We examined the frequency of the Taq-I and Bsm-I polymorphisms of the vitamin D receptor (VDR) gene in 69 patients with MS and 81 age and sex-matched healthy individuals. Genotyping of Taq-I (rs731236) and Bsm-I (rs1544410) was performed using TaqMan SNP Genotyping Assay. All patients and controls had determination of body mass index (BMI), bone mineral density (BMD) and smoking history. The mean age of patients was 39 ± 10.5 years compared to 38.7 ± 10.7 years of the controls (p = 0.86), the BMI was 24.8 ± 4.2 kg/m2 compared to 25.7 ± 4.8 kg/m2 of the controls (p = 0.23), the BMD in the lumbar spine 0.981 ± 0.15 compared to 1.025 ± 013 of the controls (p = 0.06) and the total hip BMD was 0.875 ± 0.14 compared to 0.969 ± 0.12 of the controls (p < 0.001). There were no differences of the Taq-I (TT, CT, CC) and Bsm-I genotypes (GG, GA, AA) and allelic frequencies between MS and control individuals. Multivariate analysis also failed to show any association of the Taq-I and Bsm-I polymorphisms and MS or sex, BMI, BMD and smoking history. This study suggests that the Taq-I and Bsm-I polymorphisms of the VDR gene are not associated with MS risk, BMI or BMD in the Greek population studied.
    Journal of Negative Results in BioMedicine 05/2011; 10(1):3. DOI:10.1186/1477-5751-10-3 · 1.47 Impact Factor
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    • "Recent data suggest that higher sunlight exposure and/or vitamin D supplementation in childhood may decrease the risk of MS, suggesting that this is the environmental factor implicated in the development of MS.6,7 Other recent data have suggested that vitamin D has effects on immune system function and abnormal genetic loci involved in vitamin D effects have been identified in MS patients.8 "
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    ABSTRACT: The treatment of the underlying disease process causing multiple sclerosis has continued to evolve since the initial approval of interferon-beta-1b in 1993. Current emphasis is on early treatment, including treatment after a single clinical attack (clinically isolated syndrome). The assessment of which disease modifying medication to use as initial therapy has continued to remain a combination of science and the art of medicine. Equally important are the assessment of treatment failure and the subsequent choice of medication change. This article will present scientific information, as well as information about clinical decision making, about these choices, with emphasis on the changing role of glatiramer acetate in this process.
    Neuropsychiatric Disease and Treatment 06/2010; 6:329-36. DOI:10.2147/NDT.S5898 · 1.74 Impact Factor
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