The Guanine-Thymine Dinucleotide Repeat Polymorphism Within the Tenascin-C Gene Is Associated With Achilles Tendon Injuries

Abstract

Background: Although there is a high incidence of tendon injury as a result of participation in physical activity, the mechanisms responsible for such injuries are poorly understood. Investigators have suggested that some people may have a genetic predisposition to develop tendon injuries; in particular, genes on the tip of the long arm of chromosome 9 might, at least in part, be associated with this condition. The tenascin-C gene, which has been mapped to chromosome 9q32-q34, encodes for a structural component of tendons.

Hypothesis: The tenascin-C gene is associated with Achilles tendon injury.

Study Design: Case control study; Level of evidence, 3.

Methods: A total of 114 physically active white subjects with symptoms of Achilles tendon injury and 127 asymptomatic, physically active white control subjects were genotyped for the guanine-thymine dinucleotide repeat polymorphism within the tenascin-C gene.

Results: A significant difference in the allele frequencies of this polymorphism existed between the 2 groups of subjects (χ2 = 51.0, P = .001). The frequencies of the alleles containing 12 repeats (symptomatic group, 18.9% vs control group, 10.2%) and 14 repeats (symptomatic group, 9.2% vs control group, 0.8%) were significantly higher in the symptomatic group, while the frequencies of the alleles containing 13 repeats (symptomatic group, 8.8% vs control group, 24.0%) and 17 repeats (symptomatic group, 7.5% vs control group, 20.1%) were significantly lower in this same group. Subjects who were homozygous or heterozygous for the underrepresented alleles (13 and 17 repeats) but who did not possess an overrepresented allele (12 and 14 repeats) may have a lower risk of developing Achilles tendon injuries (odds ratio, 6.2; 95% confidence interval, 3.5-11.0; P < .001).

Conclusions: The guanine-thymine dinucleotide repeat polymorphism within the tenascin-C gene is associated with Achilles tendon injury. Alleles containing 12 and 14 guanine-thymine repeats were overrepresented in subjects with tendon injuries, while the alleles containing 13 and 17 repeats were underrepresented.

Clinical Relevance: Persons who have variants of the tenascin-C gene with 12 and 14 guanine-thymine repeats appear to have a 6-fold risk of developing Achilles tendon injuries.

Keywords

genetics tendinopathy rupture risk factor

Get full access to this article

View all access options for this article.

References

Alfredson H

Lorentzon M

Backman S

Backman A

Lerner UH

. cDNA-arrays and real-time quantitative PCR techniques in the investigation of chronic Achilles tendinosis. J Orthop Res. 2003;21:970-975.

Årøen A

Helgø D

Granlund OG

Bahr R

. Contralateral tendon rupture risk is increased in individuals with a previous Achilles tendon rupture. Scand J Med Sci Sports. 2004;14:30-33.

Bennett EP

Steffensen R

Clausen H

Weghuis DO

, Geurts van Kessel A. Genomic cloning of the human histo-blood group ABO locus. Biochem Biophys Res Commun. 1995;206:18-25.

Birk DE

. Type V collagen: heterotypic type I/V collagen interactions in the regulation of fibril assembly [review]. Micron. 2001;32:223-237.

Bosman FT

Stamenkovic I

. Functional structure and composition of the extracellular matrix [review]. J Pathol. 2003;200:423-428.

Chiquet M.

Regulation of extracellular matrix gene expression by mechanical stress [review]. Matrix Biol. 1999;18:417-426.

Chiquet M

Fambrough DM

. Chick myotendinous antigen, I: a monoclonal antibody as a marker for tendon and muscle morphogenesis. J Cell Biol. 1984;98:1926-1936.

Chiquet M

Fambrough DM

. Chick myotendinous antigen, II: a novel extracellular glycoprotein complex consisting of large disulfide-linked subunits. J Cell Biol. 1984;98:1937-1946.

Chiquet M

Renedo AS

Huber F

Fluck M

. How do fibroblasts translate mechanical signals into changes in extracellular matrix production? [review]. Matrix Biol. 2003;22:73-80.

10.

Chiquet-Ehrismann R

Chiquet M

. Tenascins: regulation and putative functions during pathological stress [review]. J Pathol. 2003;200:488-499.

11.

Ireland D

Harrall R

Curry V

et al.

Multiple changes in gene expression in chronic human Achilles tendinopathy. Matrix Biol. 2001;20:159-169.

12.

Järvinen TA

Jozsa L

Kannus P

et al.

Mechanical loading regulates tenascin-C expression in the osteotendinous junction. J Cell Sci. 1999;112(pt 18):3157-3166.

13.

Järvinen TA

Jozsa L

Kannus P

et al.

Mechanical loading regulates the expression of tenascin-C in the myotendinous junction and tendon but does not induce de novo synthesis in the skeletal muscle. J Cell Sci. 2003;116:857-866.

14.

Jones FS

Jones PL

. The tenascin family of ECM glycoproteins: structure, function, and regulation during embryonic development and tissue remodeling [review]. Dev Dyn. 2000;218:235-259.

15.

Jones PL

Jones FS

. Tenascin-C in development and disease: gene regulation and cell function [review]. Matrix Biol. 2000;19:581-596.

16.

Jozsa L

Balint JB

Kannus P

Reffy A

Barzo M

. Distribution of blood groups in patients with tendon rupture: an analysis of 832 cases. J Bone Joint Surg Br. 1989;71:272-274.

17.

Jozsa L

Kvist M

Balint BJ

et al.

The role of recreational sport activity in Achilles tendon rupture: a clinical, pathoanatomical, and sociological study of 292 cases. Am J Sports Med. 1989;17:338-343.

18.

Kader D

Saxena A

Movin T

Maffulli N

. Achilles tendinopathy: some aspects of basic science and clinical management [review]. Br J Sports Med. 2002;36:239-249.

19.

Kannus P

Natri A

. Etiology and pathophysiology of tendon ruptures in sports. Scand J Med Sci Sports. 1997;7:107-112.

20.

Kujala UM

Järvinen M

Natri A

et al.

ABO blood groups and musculoskeletal injuries. Injury. 1992;23:131-133.

21.

Kvist, M.

Achilles tendon injuries in athletes [review]. Sports Med. 1994;18:173-201.

22.

Lahiri DK

Nurnberger JI Jr.

A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res. 1991;19:5444.

23.

Leppilahti J

Orava S

. Total Achilles tendon rupture: a review. Sports Med. 1998;25:79-100.

24.

Mackie EJ

. Molecules in focus: tenascin-C [review]. Int J Biochem Cell Biol. 1997;29:1133-1137.

25.

Maffulli N

Kenward MG

Testa V

Capasso G

Regine R

King JB

. Clinical diagnosis of Achilles tendinopathy with tendinosis. Clin J Sport Med. 2003;13:11-15.

26.

Murrell GA

. Understanding tendinopathies. Br J Sports Med. 2002;36:392-393.

27.

Ozelius L

Schuback DE

Stefansson K

Slaugenhaupt S

Gusella JF

Breakefield XO

. Dinucleotide repeat polymorphism for the hexabrachion gene (HXB) on chromosome 9q32-34. Hum Mol Genet. 1992;1:141.

28.

Paavola M

Kannus P

Järvinen TA

Khan K

Jozsa L

Järvinen M

. Achilles tendinopathy [review]. J Bone Joint Surg Am. 2002;84:2062-2076.

29.

Riley G.

The pathogenesis of tendinopathy: a molecular perspective [review]. Rheumatology (Oxford). 2004;43:131-142.

30.

Riley GP

Harrall RL

Cawston TE

Hazleman BL

Mackie EJ

. Tenascin-C and human tendon degeneration. Am J Pathol. 1996;149:933-943.

31.

Rocchi M

Archidiacono N

Romeo G

Saginati M

Zardi L

. Assignment of the gene for human tenascin to the region q32-q34 of chromosome 9. Hum Genet. 1991;86:621-623.

32.

Schepsis AA

Jones H

Haas AL

. Achilles tendon disorders in athletes [review]. Am J Sports Med. 2002;30:287-305.

33.

Sham PC

Curtis D

. Monte Carlo tests for associations between disease and alleles at highly polymorphic loci. Ann Hum Genet. 1995;59:97-105.

34.

Silver FH

Freeman JW

Seehra GP

. Collagen self-assembly and the development of tendon mechanical properties [review]. J Biomech. 2003;36:1529-1553.