title: Vitamin D3 receptor ( VDR ) gene rs2228570 (Fok1) and rs731236 (Taq1) variants are not associated with the risk for multiple sclerosis: results of a new study and a meta-analysis.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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 (http://www.hrc.es/investigacion/metadisc.html; 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Extremadura, Cáceres, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
authors.forename: José A G
authors.initials: JA
authors.lastname: Agúndez
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Julián
authors.initials: J
authors.lastname: Benito-León
authors.forename: Jorge
authors.initials: J
authors.lastname: Millán-Pascual
authors.forename: Patricia
authors.initials: P
authors.lastname: Calleja
authors.forename: María
authors.initials: M
authors.lastname: Díaz-Sánchez
authors.forename: Diana
authors.initials: D
authors.lastname: Pisa
authors.forename: Laura
authors.initials: L
authors.lastname: Turpín-Fenoll
authors.forename: Hortensia
authors.initials: H
authors.lastname: Alonso-Navarro
authors.forename: Lucía
authors.initials: L
authors.lastname: Ayuso-Peralta
authors.forename: Dolores
authors.initials: D
authors.lastname: Torrecillas
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Plaza-Nieto
authors.forename: Félix Javier
authors.initials: FJ
authors.lastname: Jiménez-Jiménez
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000737:chemistry; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D012306:Risk
chemical_list: D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D018167:Receptors, Calcitriol; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases