title: Contribution of VDR polymorphisms to type 1 diabetes susceptibility: Systematic review of case-control studies and meta-analysis.
abstract: Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in type 1 diabetes (T1D). However, the results are inconsistent and inconclusive. The current study aimed to investigate the role of TaqI, BsmI, ApaI and FokI VDR polymorphisms in T1D disease. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a systematic search and meta-analysis of the literature, since 1998 until december 2013, was conducted. Subgroup analyses were performed to detect potential sources of heterogeneity from selected study characteristics. Meta-analyses yielded a non-significant association of TaqI polymorphism with T1D [OR=1.014 (0.783-1.312); P=0.918] in the recessive model. The BsmI polymorphism was not associated with T1D [OR=1.44 (0.944-1.386); P=0.171] in the dominant model. Also, ApaI polymorphism was not associated with T1D risk [OR=0.996 (0.859-1.155); P=0.960] in the homozygous model. The FokI polymorphism was not associated with T1D risk [OR=0.968 (0.743-1.263); P=0.813] in dominant model. Stratification according to study characteristics showed that publication year, age, gender, estimated vitamin D levels and latitude moderated significantly association between VDR polymorphisms and T1D disease. Meta-analysis on haplotypes revealed that BAT might be a significant risk factor for T1D [OR=1.331 (0.957-1.850; P=0.089]. However, the bAT was found to be a significant protective factor [OR=0.639 (0.460-0.887); P=0.007]. As conclusion, individual VDR polymorphisms seemed not to be associated with T1D risk. However, haplotypes contributed significantly to disease susceptibility. Study characteristics moderated the association between VDR polymorphisms and T1D. These results suggested that, in T1D pathogenesis, VDR polymorphisms interact with each other and with environmental factors.
authors.affiliation: Tunis El Manar University, Faculty of Medicine Tunis, Division of Histology and Immunology Department of Basic Sciences, 15 Rue Djebel Lakdar, 1007 Tunis, Tunisia. Electronic address: kalthoum.tizaoui@yahoo.com.
authors.forename: Kalthoum
authors.initials: K
authors.lastname: Tizaoui
authors.affiliation: Tunis El Manar University, Faculty of Medicine Tunis, Division of Histology and Immunology Department of Basic Sciences, 15 Rue Djebel Lakdar, 1007 Tunis, Tunisia.
authors.forename: Wajih
authors.initials: W
authors.lastname: Kaabachi
authors.affiliation: Tunis El Manar University, Faculty of Medicine Tunis, Division of Histology and Immunology Department of Basic Sciences, 15 Rue Djebel Lakdar, 1007 Tunis, Tunisia; Abderrahmane Mami Hospital, Pediatric Pneumology Pavillon B Ariana, Tunisia.
authors.forename: Agnès
authors.initials: A
authors.lastname: Hamzaoui
authors.affiliation: Tunis El Manar University, Faculty of Medicine Tunis, Division of Histology and Immunology Department of Basic Sciences, 15 Rue Djebel Lakdar, 1007 Tunis, Tunisia.
authors.forename: Kamel
authors.initials: K
authors.lastname: Hamzaoui
mesh_terms: D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol
keywords: ApaI; BsmI; Meta-analysis; TaqI and FokI VDR polymorphisms; Type 1 diabetes