Basic Science

The TRP2 Allele of COL9A2 is an Age-Dependent Risk Factor for the Development and Severity of Intervertebral Disc Degeneration

Jim, Jeffrey J. T. PhD*†; Noponen-Hietala, Noora MD, PhD‡¶; Cheung, Kenneth M. C. FRCS†; Ott, Jürg PhD∥; Karppinen, Jaro MD, PhD#**; Sahraravand, Ahmad‡; Luk, Keith D. K. FRACS†; Yip, Shea-Ping PhD††; Sham, Pak C. MD‡‡; Song, You-Qiang PhD*†; Leong, John C. Y. FRCS†; Cheah, Kathryn S. E. PhD*; Ala-Kokko, Leena MD, PhD‡§¶; Chan, Danny PhD*

Author Information

From the Departments of *Biochemistry and †Orthopaedics and Traumatology, University of Hong Kong, Pokfulam, Hong Kong, China; ‡Center for Gene Therapy and §Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA; ∥Laboratory of Statistical Genetics, Rockefeller University, New York, NY; ¶Collagen Research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, and #Department of Physical Medicine and Rehabilitation, University of Oulu, and Finnish Institute of Occupational Health, Oulu, Finland; **Orton Orthopaedic Hospital, Helsinki, Finland; ††Department of Health Technology and Information, Hong Kong Polytechnic University, Hong Kong, China; and ‡‡Institute of Psychiatry, London University, London, United Kingdom.

J.J.T.J., N.N.-H., and K.M.C.C. contributed equally to this study.

The present affiliation of John C.Y. Leong is the Open University of Hong Kong, Hong Kong.

Acknowledgment date: October 8, 2004. First revision date: January 14, 2005. Acceptance date: January 14, 2005.

Supported by grants from the Research Grants Council of Hong Kong (HKU7230/01 M) to (K.M.C.C.) and the University Grants Committee of Hong Kong (AoE/M-04/04) (to K.S.E.C.), the Academy of Finland, the National Institutes of Health (AR45982), the Louisiana Gene Therapy Research Consortium (New Orleans, LA), and HCA-The Health Care Company (Nashville, TN) (to L.A.-K.), and the National Human Genome Research Institute (HG00008) (to J.O.).

The manuscript submitted does not contain information about medical device(s)/drug(s).

Federal, Institutional, and Other funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Address correspondence and reprint requests to Danny Chan, PhD, Department of Biochemistry, University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong; E-mail: [email protected]

Spine 30(24):p 2735-2742, December 15, 2005. | DOI: 10.1097/01.brs.0000190828.85331.ef

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 α-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.

© 2005 Lippincott Williams & Wilkins, Inc.

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