Tags

Type your tag names separated by a space and hit enter

Vitamin D receptor (VDR) gene SNPs influence VDR expression and modulate protection from multiple sclerosis in HLA-DRB1*15-positive individuals.
Brain Behav Immun 2011; 25(7):1460-7BB

Abstract

Multiple sclerosis (MS) is an autoimmune disease with a multifactorial etiology. The HLA-DRB1*15 allele, is the main genetic risk factor for MS in Caucasians; recent findings showed that the transcription of this molecule is regulated by the vitamin D/vitamin D receptor (VDR) complex. We analyzed SNPs within the VDR gene in association with the HLA-DRB1 locus in 641 MS patients diagnosed according to McDonald criteria and 558 age- and sex-matched healthy controls, to verify possible correlations between the vitamin D/VDR complex, HLA-DRB1, and susceptibility to MS. Results confirmed that HLA-DRB1*15 is a strong predisposing allele (p<1×10(-7); OR: 3.04; 95% CI: 2.02-4.60) for MS. Cosegregation analyses of VDR SNPs with HLA-DRB1*15 indicated a reduction of risk for MS given by the presence of the -DRB1*15-rs731236 T VDR haplotype (p=9.5×10(-5); OR: 2.52; 95% CI: 1.56-4.06) and, conversely, an augmented risk for disease associated with the -DRB1*15-rs731236 C VDR haplotype. Analyses performed on HLA-DRB1*15-positive MS patients and HC alone confirmed the protective role of rs731236 TT VDR genotype (p(y)=0.004; OR: 0.53; 95% CI: 0.33-0.83); notably, FACS, PCR, and confocal microscopy analyses showed that rs731236 TT genotype is associated with an augmented VDR expression in MBP-stimulated PBMC from patients. In conclusion, rs731236 TT VDR genotype modulates VDR expression and confers protection against MS in HLA-DRB1*15-positive individuals. Results herein offer a model justifying the interaction between the major genetic (HLA-DRB*15) and environmental (vitamin D) factors associated with MS onset.

Authors+Show Affiliations

Don C. Gnocchi Foundation ONLUS, P.le Morandi 6, 20121 Milan, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21664963

Citation

Agliardi, Cristina, et al. "Vitamin D Receptor (VDR) Gene SNPs Influence VDR Expression and Modulate Protection From Multiple Sclerosis in HLA-DRB1*15-positive Individuals." Brain, Behavior, and Immunity, vol. 25, no. 7, 2011, pp. 1460-7.
Agliardi C, Guerini FR, Saresella M, et al. Vitamin D receptor (VDR) gene SNPs influence VDR expression and modulate protection from multiple sclerosis in HLA-DRB1*15-positive individuals. Brain Behav Immun. 2011;25(7):1460-7.
Agliardi, C., Guerini, F. R., Saresella, M., Caputo, D., Leone, M. A., Zanzottera, M., ... Clerici, M. (2011). Vitamin D receptor (VDR) gene SNPs influence VDR expression and modulate protection from multiple sclerosis in HLA-DRB1*15-positive individuals. Brain, Behavior, and Immunity, 25(7), pp. 1460-7. doi:10.1016/j.bbi.2011.05.015.
Agliardi C, et al. Vitamin D Receptor (VDR) Gene SNPs Influence VDR Expression and Modulate Protection From Multiple Sclerosis in HLA-DRB1*15-positive Individuals. Brain Behav Immun. 2011;25(7):1460-7. PubMed PMID: 21664963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D receptor (VDR) gene SNPs influence VDR expression and modulate protection from multiple sclerosis in HLA-DRB1*15-positive individuals. AU - Agliardi,Cristina, AU - Guerini,Franca R, AU - Saresella,Marina, AU - Caputo,Domenico, AU - Leone,Maurizio A, AU - Zanzottera,Milena, AU - Bolognesi,Elisabetta, AU - Marventano,Ivana, AU - Barizzone,Nadia, AU - Fasano,Maria E, AU - Al-Daghri,Nasser, AU - Clerici,Mario, Y1 - 2011/06/12/ PY - 2011/04/22/received PY - 2011/05/26/revised PY - 2011/05/26/accepted PY - 2011/6/14/entrez PY - 2011/6/15/pubmed PY - 2012/1/17/medline SP - 1460 EP - 7 JF - Brain, behavior, and immunity JO - Brain Behav. Immun. VL - 25 IS - 7 N2 - Multiple sclerosis (MS) is an autoimmune disease with a multifactorial etiology. The HLA-DRB1*15 allele, is the main genetic risk factor for MS in Caucasians; recent findings showed that the transcription of this molecule is regulated by the vitamin D/vitamin D receptor (VDR) complex. We analyzed SNPs within the VDR gene in association with the HLA-DRB1 locus in 641 MS patients diagnosed according to McDonald criteria and 558 age- and sex-matched healthy controls, to verify possible correlations between the vitamin D/VDR complex, HLA-DRB1, and susceptibility to MS. Results confirmed that HLA-DRB1*15 is a strong predisposing allele (p<1×10(-7); OR: 3.04; 95% CI: 2.02-4.60) for MS. Cosegregation analyses of VDR SNPs with HLA-DRB1*15 indicated a reduction of risk for MS given by the presence of the -DRB1*15-rs731236 T VDR haplotype (p=9.5×10(-5); OR: 2.52; 95% CI: 1.56-4.06) and, conversely, an augmented risk for disease associated with the -DRB1*15-rs731236 C VDR haplotype. Analyses performed on HLA-DRB1*15-positive MS patients and HC alone confirmed the protective role of rs731236 TT VDR genotype (p(y)=0.004; OR: 0.53; 95% CI: 0.33-0.83); notably, FACS, PCR, and confocal microscopy analyses showed that rs731236 TT genotype is associated with an augmented VDR expression in MBP-stimulated PBMC from patients. In conclusion, rs731236 TT VDR genotype modulates VDR expression and confers protection against MS in HLA-DRB1*15-positive individuals. Results herein offer a model justifying the interaction between the major genetic (HLA-DRB*15) and environmental (vitamin D) factors associated with MS onset. SN - 1090-2139 UR - https://www.unboundmedicine.com/medline/citation/21664963/Vitamin_D_receptor__VDR__gene_SNPs_influence_VDR_expression_and_modulate_protection_from_multiple_sclerosis_in_HLA_DRB1_15_positive_individuals_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0889-1591(11)00196-6 DB - PRIME DP - Unbound Medicine ER -