STUDY DESIGN: 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. OBJECTIVES: To gain a better understanding of the etiology of DDD in relation to structural defects of the intervertebral disc. SUMMARY OF BACKGROUND DATA: 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. CONCLUSION: 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.
STUDY DESIGN: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. OBJECTIVES: To gain a better understanding of the etiology of DDD in relation to structural defects of the intervertebral disc. SUMMARY OF BACKGROUND DATA: 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. CONCLUSION: 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: I M Virtanen; Y Q Song; K M C Cheung; L Ala-Kokko; J Karppinen; D W H Ho; K D K Luk; S P Yip; J C Y Leong; K S E Cheah; P Sham; D Chan Journal: J Med Genet Date: 2007-01-12 Impact factor: 6.318
Authors: Tue Secher Jensen; Jaro Karppinen; Joan S Sorensen; Jaakko Niinimäki; Charlotte Leboeuf-Yde Journal: Eur Spine J Date: 2008-09-12 Impact factor: 3.134
Authors: Kyle D Allen; Timothy M Griffin; Ramona M Rodriguiz; William C Wetsel; Virginia B Kraus; Janet L Huebner; Lawrence M Boyd; Lori A Setton Journal: Arthritis Rheum Date: 2009-09
Authors: You-Qiang Song; Tatsuki Karasugi; Kenneth M C Cheung; Kazuhiro Chiba; Daniel W H Ho; Atsushi Miyake; Patrick Y P Kao; Kit Ling Sze; Anita Yee; Atsushi Takahashi; Yoshiharu Kawaguchi; Yasuo Mikami; Morio Matsumoto; Daisuke Togawa; Masahiro Kanayama; Dongquan Shi; Jin Dai; Qing Jiang; Chengai Wu; Wei Tian; Na Wang; John C Y Leong; Keith D K Luk; Shea-ping Yip; Stacey S Cherny; Junwen Wang; Stefan Mundlos; Anthi Kelempisioti; Pasi J Eskola; Minna Männikkö; Pirkka Mäkelä; Jaro Karppinen; Marjo-Riitta Järvelin; Paul F O'Reilly; Michiaki Kubo; Tomoatsu Kimura; Toshikazu Kubo; Yoshiaki Toyama; Hiroshi Mizuta; Kathryn S E Cheah; Tatsuhiko Tsunoda; Pak-Chung Sham; Shiro Ikegawa; Danny Chan Journal: J Clin Invest Date: 2013-11 Impact factor: 14.808
Authors: Uruj Zehra; Cora Bow; Jeffrey C Lotz; Frances M K Williams; S Rajasekaran; Jaro Karppinen; Keith D K Luk; Michele C Battiê; Dino Samartzis Journal: Eur Spine J Date: 2017-09-12 Impact factor: 3.134
Authors: Jillian E Mayer; James C Iatridis; Danny Chan; Sheeraz A Qureshi; Omri Gottesman; Andrew C Hecht Journal: Spine J Date: 2013-03 Impact factor: 4.166