This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (82)  • Contact me when this article is cited  Related Content  • Related articles  • Similar articles in JAMA  Topic Collections  • Genetics  • Genetic Counseling/ Testing/ Therapy  • Genetic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Petteri Paassilta, MD,PhD; Jaana Lohiniva; Harald H. H. Göring, PhD; Merja Perälä, PhD; S. Susanna Räinä; Jaro Karppinen, MD; Markku Hakala, MD,PhD; Tiina Palm, MD; Heikki Kröger, MD,PhD; Ilkka Kaitila, MD,PhD; Heikki Vanharanta, MD,PhD; Jürg Ott, PhD; Leena Ala-Kokko, MD,PhD

JAMA. 2001;285:1843-1849.

Context  Lumbar disk disease (LDD) is one of the most common musculoskeletal diseases, with a prevalence of about 5%. A tryptophan (Trp) allele (Trp2) was recently discovered in the COL9A2 gene that is associated with dominantly inherited LDD but is only present in about 4% of Finnish patients with LDD.

Objective  To determine if other collagen IX gene sequence variations play a role in the pathogenesis of LDD.

Design and Setting  Case-control study conducted from February 1997 to May 1998 at university hospitals in Finland.

Participants  A total of 171 individuals with LDD (evaluated clinically and by magnetic resonance imaging or computed tomography) and 321 controls without LDD (186 healthy individuals, 83 patients with primary osteoarthritis, 31 with rheumatoid arthritis, and 21 with chondrodysplasias).

Main Outcome Measures  Frequencies of sequence variations covering the entire coding sequences and exon boundaries of the collagen IX genes, COL9A1, COL9A2, and COL9A3, which code for the 1, 2, and 3 chains of the protein, detected by conformation-sensitive gel electrophoresis and confirmed by sequencing, compared between individuals with and without LDD.

Results  Mutation analysis of all 3 collagen IX genes resulted in identification of an Arg103Trp (argininetryptophan) substitution in the 3 chain (Trp3 allele). The frequency of the Trp3 allele was 12.2% in LDD cases, excluding 7 individuals who were carriers of the previously identified Gln326Trp (glutaminetryptophan) substitution in the 2 chain (Trp2 allele), and was 4.7% among controls. The difference in the frequency was statistically significant (P = .000013). Presence of at least 1 Trp3 allele increases risk of LDD about 3-fold.

Conclusion  This study led to the identification of a novel common genetic risk factor for LDD, confirming that genetic risk factors likely play a significant role in LDD.

Author Affiliations: Collagen Research Unit, Biocenter, and Departments of Medical Biochemistry (Drs Paassilta, Perälä, and Ala-Kokko and Mss Lohiniva and Räinä), Physical Medicine and Rehabilitation (Drs Karppinen and Vanharanta), and Internal Medicine (Dr Hakala), University of Oulu, Oulu, Finland; Department of Genetics and Development, Columbia University, New York, NY (Drs Göring and Ott); Department of Surgery, University of Kuopio, Kuopio, Finland (Drs Palm and Kröger); Department of Clinical Genetics, Helsinki University Hospital, Helsinki, Finland (Dr Kaitila); Laboratory of Statistical Genetics, Rockefeller University, New York, NY (Dr Ott); Center for Gene Therapy, Medical College of Pennsylvania/Hahnemann University, Philadelphia (Dr Ala-Kokko). Dr Göring is now with the Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Tex; Dr Ala-Kokko is now with the Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, La.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

RELATED ARTICLES

Genetic Risk Factors for Lumbar Disk Disease
Joan C. Marini
JAMA. 2001;285(14):1886-1888.
EXTRACT | FULL TEXT  

April 11, 2001
JAMA. 2001;285(14):1903-1904.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

The pathophysiology of disc degeneration: A CRITICAL REVIEW
Hadjipavlou et al.
J Bone Joint Surg Br 2008;90-B:1261-1270.
ABSTRACT | FULL TEXT  

Lumbar Degenerative Disk Disease
Modic and Ross
Radiology 2007;245:43-61.
ABSTRACT | FULL TEXT  

Phenotypic and population differences in the association between CILP and lumbar disc disease
Virtanen et al.
J. Med. Genet. 2007;44:285-288.
ABSTRACT | FULL TEXT  

Association of a COL1A1 polymorphism with lumbar disc disease in young military recruits
Tilkeridis et al.
J. Med. Genet. 2005;42:e44-e44.
ABSTRACT | FULL TEXT  

Intervertebral Disc Degeneration: The Role of the Mitochondrial Pathway in Annulus Fibrosus Cell Apoptosis Induced by Overload
Rannou et al.
Am. J. Pathol. 2004;164:915-924.
ABSTRACT | FULL TEXT  

Sequence variations in the collagen IX and XI genes are associated with degenerative lumbar spinal stenosis
Noponen-Hietala et al.
Ann Rheum Dis 2003;62:1208-1214.
ABSTRACT | FULL TEXT  

Intervertebral Disc Collagen: USAGE OF THE SHORT FORM OF THE {alpha}1(IX) CHAIN IN BOVINE NUCLEUS PULPOSUS
Wu and Eyre
J. Biol. Chem. 2003;278:24521-24525.
ABSTRACT | FULL TEXT  

Radiologic Phenotypes in Lumbar MR Imaging for a Gene Defect in the COL9A3 Gene of Type IX Collagen
Karppinen et al.
Radiology 2003;227:143-148.
ABSTRACT | FULL TEXT  

The Association of Lumbar Disc Disease with Vitamin-D Receptor Gene Polymorphism
Kawaguchi et al.
JBJS 2002;84:2022-2028.
ABSTRACT | FULL TEXT  

Genomes, Neuroscience, and Neurology
Pulst
Arch Neurol 2001;58:1755-1757.
FULL TEXT  

Collagen IX Mutation Associated with Back Pain
JWatch General 2001;2001:3-3.
FULL TEXT  

Genetic Risk Factors for Lumbar Disk Disease
Marini
JAMA 2001;285:1886-1888.
FULL TEXT