title: The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration.
abstract: METHODS
  Low back pain (LBP) and sciatica are usually caused by degenerative disc disease (DDD). Although they are common, the etiology of these conditions is poorly understood. A large population case-control study in the Southern Chinese was performed to study genetic risk factors to DDD.
  
  
  OBJECTIVE
  To gain a better understanding of the etiology of DDD in relation to structural defects of the intervertebral disc.
  
  
  BACKGROUND
  A Finnish study found an association between LBP and sciatica with two variants of the alpha-chains of collagen IX, encoded by the Trp2 and Trp3 alleles, representing Gln326Trp and Arg103Trp amino acid substitutions in the COL9A2 and COL9A3 genes, respectively. Trp2 was found only in affected individuals (4%), whereas Trp3 was present in both affected (24%) and unaffected (9%) individuals. Because of the low frequency of the Trp2 allele in whites, the significance and contribution of this allele to DDD are not known. Using more objective criteria to define the disease by magnetic resonance imaging (MRI), we tested these alleles for association with DDD in a large population study.
  
  
  METHODS
  Lumbar DDD, the presence of anular tears, and disc and endplate herniations were defined by MRI in 804 Southern Chinese volunteers 18 to 55 years of age. These were correlated with the frequencies of the Trp2 and Trp3 alleles.
  
  
  RESULTS
  The Trp2 allele was present in 20% of the population and was associated with a fourfold increase in the risk of developing anular tears at 30 to 39 years and a 2.4-fold increase in the risk of developing DDD and endplate herniations at 40 to 49 years. Affected Trp2 individuals had more severe degeneration. The Trp3 allele was absent from the Southern Chinese population.
  
  
  CONCLUSIONS
  This largest-ever population study using MRI to define DDD demonstrates for the first time that the Trp2 allele is a significant risk factor for the development and severity of degeneration. The association is age- dependent as it is more prevalent in some age groups than in others. The contrasting Trp allele frequencies between the Finns and the Chinese are the first indication that the genetic risk factors for DDD varies between ethnic groups.
authors.affiliation: Department of Biochemistry, University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Jeffrey J T
authors.initials: JJ
authors.lastname: Jim
authors.forename: Noora
authors.initials: N
authors.lastname: Noponen-Hietala
authors.forename: Kenneth M C
authors.initials: KM
authors.lastname: Cheung
authors.forename: Jürg
authors.initials: J
authors.lastname: Ott
authors.forename: Jaro
authors.initials: J
authors.lastname: Karppinen
authors.forename: Ahmad
authors.initials: A
authors.lastname: Sahraravand
authors.forename: Keith D K
authors.initials: KD
authors.lastname: Luk
authors.forename: Shea-Ping
authors.initials: SP
authors.lastname: Yip
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
authors.forename: You-Qiang
authors.initials: YQ
authors.lastname: Song
authors.forename: John C Y
authors.initials: JC
authors.lastname: Leong
authors.forename: Kathryn S E
authors.initials: KS
authors.lastname: Cheah
authors.forename: Leena
authors.initials: L
authors.lastname: Ala-Kokko
authors.forename: Danny
authors.initials: D
authors.lastname: Chan
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D024081:Collagen Type IX / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007403:Intervertebral Disc / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012720:Severity of Illness Index; D013122:Spinal Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology*
chemical_list: C120282:COL9A2 protein, human; D024081:Collagen Type IX