title: Association Between the FokI and ApaI Polymorphisms in the Vitamin D Receptor Gene and Intervertebral Disc Degeneration: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Evidence supporting an association of intervertebral disc degeneration (DD) with polymorphisms of the vitamin D receptor (VDR) gene has been controversial. We performed a meta-analysis of these studies to determine if there was substantial evidence to support such an association between the VDR polymorphisms and DD.
  
  
  METHODS
  PubMed, Embase, and Science Direct databases were searched for studies that investigated associations of the FokI (rs2228570, rs10735810), and ApaI (rs7975253) polymorphisms of the VDR gene with DD. From the extracted genotype data from 14 publications, we estimated risk (odds ratio [OR] with 95% confidence intervals).
  
  
  RESULTS
  Overall associations of FokI with DD were absent (OR 0.96-1.04, p = 0.73-0.95) with heterogeneity in the dominant and codominant models (pheteroegeneity<0.10, I2= 47-57%). Post-outlier pooled effects yielded dominant significance indicating reduced risk (OR 0.77, p = 0.01) with concomitant zero heterogeneity (I2= 0%). ApaI effects pointed to reduced risks, with overall dominant significance (OR 0.69, p = 0.04) and Asian subgroup nonsignificance (OR 0.75-0.93, p = 0.17-0.74). In FokI, Non-Hispanic Caucasians (OR 0.77, p = 0.01) and males (OR 0.36-0.66, p = 0.001-0.04) were protected but not Hispanic Caucasians (OR 1.39-1.85, p = 0.006-0.05) and females (OR 1.72, p = 0.05). Tests of interaction between the genders highlighted female susceptibility and male protection (p = 0.001-0.005). Zero heterogeneity (I2= 0%) is a key strength of these significant effects.
  
  
  CONCLUSIONS
  This meta-analysis confirmed the protective role of the ApaI polymorphism, however, susceptibility and protective effects of the FokI polymorphism may be ethnic and gender specific.
authors: 1 Center for Research and Development, Angeles University Foundation , Angeles City, Philippines .
authors: Noel
authors: N
authors: Pabalan
authors: 2 Department of Biological Sciences, Angeles University Foundation , Angeles City, Philippines .
authors: Lani
authors: L
authors: Tabangay
authors: 3 Environmental Monitoring and Reporting Branch, Ontario Ministry of the Environment and Climate Change , Etobicoke, Canada .
authors: Hamdi
authors: H
authors: Jarjanazi
authors: 4 Orthopedics and Traumatology, Faculdade de Medicina do ABC-Santo André , São Paulo, Brazil .
authors: Luiz Angelo
authors: LA
authors: Vieira
authors: 5 Department of Collective Health, Faculdade de Medicina do ABC, Human Reproduction and Genetics Center , São Paulo, Brazil .
authors: Aline Amaro
authors: AA
authors: Dos Santos
authors: 5 Department of Collective Health, Faculdade de Medicina do ABC, Human Reproduction and Genetics Center , São Paulo, Brazil .
authors: Caio Parente
authors: CP
authors: Barbosa
authors: 4 Orthopedics and Traumatology, Faculdade de Medicina do ABC-Santo André , São Paulo, Brazil .
authors: Luciano Miller Reis
authors: LM
authors: Rodrigues
authors: 5 Department of Collective Health, Faculdade de Medicina do ABC, Human Reproduction and Genetics Center , São Paulo, Brazil .
authors: Bianca
authors: B
authors: Bianco
mesh_terms: D016022:Case-Control Studies; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific
keywords: disc degeneration; meta-analysis; polymorphisms; vitamin D receptor