title: Bone morphogenetic protein 6 polymorphisms are associated with radiographic progression in ankylosing spondylitis.
abstract: OBJECTIVE
  Nearly 25 genetic loci associated with susceptibility to ankylosing spondylitis (AS) have been identified by several large studies. However, there have been limited studies to identify the genes associated with radiographic severity of the disease. Thus we investigated which genes involved in bone formation pathways might be associated with radiographic severity in AS.
  
  
  METHODS
  A total of 417 Korean AS patients were classified into two groups based on the radiographic severity as defined by the modified Stoke' Ankylosing Spondylitis Spinal Score (mSASSS) system. Severe AS was defined by the presence of syndesmophytes and/or fusion in the lumbar or cervical spine (n = 195). Mild AS was defined by the absence of any syndesmophyte or fusion (n = 170). A total of 251 single nucleotide polymorphisms (SNPs) within 52 genes related to bone formation were selected and genotyped. Odds ratios (OR) and 95% confidence interval (95% CI) were analysed by multivariate logistic regression controlling for age at onset of symptoms, sex, disease duration, and smoking status as covariates.
  
  
  RESULTS
  We identified new loci of bone morphogenetic protein 6 (BMP6) associated with radiographic severity in patients with AS that passed false discovery rate threshold. Two SNPs in BMP6 were significantly associated with radiologic severity [rs270378 (OR 1.97, p = 6.74 × 10(-4)) and rs1235192 [OR 1.92, p = 1.17 × 10(-3)]) adjusted by covariates.
  
  
  CONCLUSIONS
  This is the first study to demonstrate that BMP6 is associated with radiographic severity in AS, supporting the role wingless-type like/BMP pathway on radiographic progression in AS.
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Joo
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Bang
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Division of Rheumatology, Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, Republic of Korea.
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Shim
authors.affiliation: Department of Radiology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Seunghun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Radiology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Kyung Bin
authors.initials: KB
authors.lastname: Joo
authors.affiliation: Department of Orthopedics, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
authors.forename: Jong Heon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of anthropology, Cornell University, Ithaca, New York, United States of America.
authors.forename: Hye Joon
authors.initials: HJ
authors.lastname: Min
authors.affiliation: Department of Rheumatology, Memorial University, St. Clare's Mercy Hospital, St. John's, Newfoundland, Canada.
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
authors.affiliation: Division of Rheumatology, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Inman
mesh_terms: D055418:Bone Morphogenetic Protein 6 / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D013167:Spondylitis, Ankylosing / Q000235:genetics*
chemical_list: C525816:BMP6 protein, human; D055418:Bone Morphogenetic Protein 6