title: GDF5 single-nucleotide polymorphism rs143383 is associated with lumbar disc degeneration in Northern European women.
abstract: OBJECTIVE
  Lumbar disc degeneration (LDD) is a serious social and medical problem which has been shown to be highly heritable. It has similarities with peripheral joint osteoarthritis (OA) in terms of both epidemiology and pathologic processes. A few known genetic variants have been identified using a candidate gene approach, but many more are thought to exist. GDF5 is a gene whose variants have been shown to play a role in skeletal height as well as predisposing to peripheral joint OA. In vitro, the gene product growth differentiation factor 5 has been shown to promote growth and repair of animal disc. This study was undertaken to investigate whether the GDF5 gene plays a role in LDD.
  
  
  METHODS
  We investigated whether the 5' upstream single-nucleotide polymorphism (SNP) variant rs143383 was associated with LDD, using plain radiography and magnetic resonance imaging to identify disc space narrowing and osteophytes, in 5 population cohorts from Northern Europe.
  
  
  RESULTS
  An association between LDD and the SNP rs143383 was identified in women, with the same risk allele as in knee and hip OA (odds ratio 1.72 [95% confidence interval 1.15-2.57], P = 0.008).
  
  
  CONCLUSIONS
  Our findings in 5 population cohorts from Northern Europe indicate that a variant in the GDF5 gene is a risk factor for LDD in women. Many more such variants are predicted to exist, but this result highlights the growth and differentiation cellular pathway as a possible route to a better understanding of the process behind lumbar disc degeneration.
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. frances.williams@kcl.ac.uk
authors.forename: F M K
authors.initials: FM
authors.lastname: Williams
authors.forename: M
authors.initials: M
authors.lastname: Popham
authors.forename: D J
authors.initials: DJ
authors.lastname: Hart
authors.forename: E
authors.initials: E
authors.lastname: de Schepper
authors.forename: S
authors.initials: S
authors.lastname: Bierma-Zeinstra
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: A G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: N K
authors.initials: NK
authors.lastname: Arden
authors.forename: C
authors.initials: C
authors.lastname: Cooper
authors.forename: T D
authors.initials: TD
authors.lastname: Spector
authors.forename: A M
authors.initials: AM
authors.lastname: Valdes
authors.forename: J
authors.initials: J
authors.lastname: van Meurs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D005060:Europe / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055428:Growth Differentiation Factor 5 / Q000235:genetics*; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011859:Radiography; D012307:Risk Factors; D055815:Young Adult
chemical_list: C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5