title: BsmI, ApaI and TaqI Polymorphisms in the Vitamin D Receptor Gene (VDR) and Association with Lumbar Spine Pathologies: An Italian Case-Control Study.
abstract: Three adjacent single nucleotide polymorphisms of the vitamin D receptor gene (VDR) BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) are commonly studied in several pathologies. We aimed to evaluate the distribution of VDR BsmI, ApaI, and TaqI allele, genotype, and haplotype frequencies in an Italian cohort of 266 patients with lumbar spine disorders assessed by Magnetic Resonance Imaging and 252 asymptomatic controls. The exposure to putative risk factors was evaluated by a questionnaire. Polymorphisms were detected by PCR-RFLP and TaqMan® SNP Genotyping Assay. The results were statistically adjusted for the identified conventional risk factors. The three SNPs were in linkage disequilibrium. For all cases BbAaTT was a 3-fold risk factor OR = 3.38), whereas bbAATT (OR = 0.22), and bbaaTT (OR = 0.47) genotypes were found to be protective. Specifically, for patients affected by disc herniation only (n = 88) and all lumbar pathologies excluding stenosis and/or spondylolistesis (n = 215) B allele, Bb, Aa, and BbAaTT genotypes were risky, whereas b allele, bb, aa, and bbaaTT genotypes were protective. In patients affected by osteochondrosis with or without disc hernation (n = 50), T allele, Aa, and bbAaTT genotypes were risky, whereas t allele, AA, tt genotypes were protective. In patients affected by stenosis and/or spondylolistesis (n = 51) no significant associations were found. This is the first study showing an association of the three genetic VDR variants BsmI, ApaI, and TaqI and lumbar spine pathologies. Our study contributes to delineate genetic risk factors for specific subgroups of patients with lumbar spine pathologies highlighting the importance of haplotype analysis, and of detailed clinical evaluation of the patients for identification of genetic biomarkers.
authors.affiliation: Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Colombini
authors.affiliation: Scoliosis Unit, Department of Orthopedics and Traumatology - Spine surgery III, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Brayda-Bruno
authors.affiliation: Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lombardi
authors.affiliation: Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italy.
authors.forename: Samantha Jennifer
authors.initials: SJ
authors.lastname: Croiset
authors.affiliation: Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ceriani
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Buligan
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Barbina
authors.affiliation: Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Banfi
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Cauci
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium / Q000235:genetics; D008159:Lumbar Vertebrae / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors; D013122:Spinal Diseases / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D018167:Receptors, Calcitriol; C579457:VDR protein, human; C053864:endodeoxyribonuclease BsmI; D015252:Deoxyribonucleases, Type II Site-Specific; C038485:GGGCCC-specific type II deoxyribonucleases; C027046:TCGA-specific type II deoxyribonucleases