title: Associations of vitamin d binding protein gene polymorphisms with the development of peripheral arthritis and uveitis in ankylosing spondylitis.
abstract: OBJECTIVE
  Genetic factors account for more than 90% of overall susceptibility to ankylosing spondylitis (AS), and recent studies have focused on non-major histocompatibility complex genes. Vitamin D binding protein (DBP) is a highly polymorphic protein that transports vitamin D and its metabolites. In addition to its sterol binding capacity, DBP has many other roles in the inflammatory and immune systems, and has been reported to be associated with autoimmune diseases. We investigated the association between DBP polymorphisms and susceptibility to AS.
  
  
  METHODS
  This case-control study was conducted in 223 patients with AS and 239 ethnically matched controls who were genotyped for 8 single-nucleotide polymorphisms (SNP) in the DBP and its promoter. Genomic DNA was isolated from peripheral blood leukocytes using the standard phenolchloroform method, and the GoldenGate assay was used for genotyping.
  
  
  RESULTS
  No significant association was found between the susceptibility to AS and DBP polymorphisms. In a subgroup analysis of patients with AS, G alleles at rs222016 and rs222020 (OR 0.63, 95% CI 0.42-0.95, p = 0.03; OR 0.63, 95% CI 0.42-0.95, p = 0.03, respectively) and A allele at rs3733359 (OR 0.59, 95% CI 0.39-0.90, p = 0.01) showed the decreased risk of peripheral arthritis. G allele at rs4752 showed increased risk of uveitis (OR 2.04, 95% CI 1.12-3.72, p = 0.02). On the haplotype analyses, haplotype 2 (AGGA) protected against the development of peripheral arthritis (p = 0.01) and haplotype 3 (GAAG) was associated with an increased likelihood of uveitis (p = 0.02).
  
  
  CONCLUSIONS
  DBP gene polymorphisms are associated with the development of peripheral arthritis and uveitis in Korean patients with AS. Given the influence of different DBP variants on the immune system, larger-scale studies are warranted to elucidate the role of DBP in the pathogenesis of AS.
authors.affiliation: Department of Medicine, Eulji University Hospital, Seogu Dunsandong 1306, 302-799, Daejeon, South Korea.
authors.forename: Kyong-Hee
authors.initials: KH
authors.lastname: Jung
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Dong-Hyuk
authors.initials: DH
authors.lastname: Sheen
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Lim
authors.forename: Sang-Kwang
authors.initials: SK
authors.lastname: Lee
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hyo
authors.initials: H
authors.lastname: Park
authors.forename: Soo-Cheon
authors.initials: SC
authors.lastname: Chae
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Shim
mesh_terms: D000328:Adult; D000483:Alleles; D001168:Arthritis / Q000209:etiology / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012307:Risk Factors; D013167:Spondylitis, Ankylosing / Q000150:complications / Q000235:genetics*; D014605:Uveitis / Q000209:etiology / Q000235:genetics*; D014809:Vitamin D-Binding Protein / Q000235:genetics*
chemical_list: D014809:Vitamin D-Binding Protein