Article Text

Association of a COL1A1 polymorphism with lumbar disc disease in young military recruits
  1. C Tilkeridis*,
  2. T Bei*,
  3. S Garantziotis,
  4. C A Stratakis
  1. Center for Recruitment of Military Personnel for Health Services (KEYG), Hellenic Armed Forces, Arta, Greece, and the Section on Genetics and Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to:
 Dr Constantine A Stratakis
 Section on Endocrinology and Genetics, DEB, NICHD, NIH, Building 10, CRC, Room I-3330, 10 Center Drive, MSC 1103, Bethesda, Maryland 20892, USA;


Background: Lumbar disc disease (LDD), one of the most common conditions for which patients seek medical care, has been associated with sequence changes of the COL genes. COL1A1, however, has not been studied in young patients with LDD; COL1A1 polymorphisms have been associated with bone mineral density (BMD) in several populations and with LDD in older adults.

Objective: To study COL1A1 polymorphisms in young Greek army recruits with LDD.

Subjects: These young soldiers were diagnosed with early LDD at the time of their presentation to a military training site. All patients had radiological confirmation of their disease; a control group was also studied.

Methods: Sp1-binding site polymorphism of the COL1A1 gene was investigated by standard methods.

Results: There was an increased frequency of the “ss” genotype (33.3%) in LDD patients; none of the controls had this genotype. In addition, a significantly smaller number of controls was heterozygotes for this allele.

Conclusions: A previously studied sequence change of the regulatory region of the COL1A1 gene, the same as has previously been associated with low BMD in many populations and LDD in older adults, showed a strong association with LDD in young male soldiers who were recently diagnosed with this disease.

  • BMD, bone mineral density
  • LDD, lumbar disc disease
  • collagen
  • spine
  • SP1

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Lumbar disc disease (LDD) is among the most common ailments in Western societies.1 In the military, LDD often results in significant impairments and contributes greatly to health care costs and disability.2 Military training often results in exacerbation or presentation of LDD related symptoms. LDD appears to be a multifactorial disorder in which genetics play an important role, as it is evident from several recent studies.3

Collagen is the most abundant structural component of the extracellular matrix. Changes in collagen cross linking have been identified in degenerative disc disease, and LDD was recently associated with a polymorphism of the collagen type IX (COL9A3) gene.3 Type I collagen is the major protein in skin, ligaments, and bone; both COL1A1 and COL1A2 are present in the main components of the intervertebral disc, the annulus fibrosus (primarily) and the nucleus pulposus (secondarily).4

A G→T polymorphism within the COL1A1 regulatory region that affects the recognition site for transcription factor Sp1 has been associated with lower bone mineral density (BMD), osteoporosis, and vertebral fractures mainly in postmenopausal populations.5 A recent paper in the Journal of Medical Genetics addressed the contribution of the Sp1 polymorphism in the determination of BMD in elderly white women.6 Although type I collagen abnormalities have been implicated in the pathogenesis of LDD,4 the Sp1 sequence alteration has not been investigated in young patients with LDD.


We collected blood from 36 Greek army recruits at the time of recruitment (during basic training), 24 with LDD (mean (SD) age, 29 (7.6) years), and 12 controls matched for body mass index (BMI) (mean age, 25 (3.8) years). All were healthy, with normal BMD and no history of trauma or fractures. The only health complaint of the patient group was low back pain. All patients had radiological confirmation of LDD by magnetic resonance imaging. The protocol was approved by the Department of Defence Health Service Review Committee, Athens, Greece.

Genomic DNA was extracted from blood samples by standard methods. To detect the G→T polymorphism, we used a polymerase chain reaction based method5; positive samples were sequenced for confirmation of the sequence change.


There was a significant difference between patients with LDD and controls: 33.3% of the patients were T/T v none of the controls (p<0.001) (table 1). In addition, a significantly smaller number of controls was heterozygotes for this allele: 66.7% in the LDD patients v 41.7% in the controls.

Table 1

 Genotyping data from patients with lumbar disc disease and controls

T is the “s” allele of the Sp1 binding site COL1A1 polymorphism which has been associated with fractures, low BMD, and BMI.5 This is the second report of a positive association between the COLA1 “s” allele and LDD; the first, however, was a study of elderly patients with other bone diseases, in which it was shown that elderly men and women with the TT genotype had a higher risk of disc degeneration than those with the GG and GT genotypes, with an odds ratio of 3.6.7

It has been shown that the production of pro-collagen type I increases in LDD, possibly as a repair mechanism.4 Consistent with this hypothesis, a recent study suggested that collagen type I in a glycosaminoglycan matrix induced proteoglycans synthesis by canine intervertebral disc cells.8 In mice genetically engineered for reduced type I collagen, vertebral disc tissue was also mechanically inferior when compared with control animals.9 It is therefore plausible that an increased ratio of COL1A1 expression compared with COL1A2—as suggested for the effect of this Sp1 binding site polymorphism5—may lead to structural alterations as well as to healing defects in the annulus fibrosus and other components of the discs in LDD.


We thank Dr Joan Marini (NICHD, NIH) for a critical review of this work and submitted text. We also thank Dr Evanggelos Kortessas, then Acting Director of the KEYG Center at Arta, Greece, for his support of the study and approval of the research protocol.


Supplementary materials

  • There is an error in the main text of this article:

    Results and discussion
    Under the Results and discussion, in the first paragraph, the second sentence reads: "In addition, a significantly smaller number of controls was heterozygotes for this allele: 66.7% in the LDD patients v 41.7% in the controls." However, corresponding to the figures in Table I, this sentence should read: "[However], a significantly greater number of controls was heterozygotes for this allele: 66.7% in the controls v 41.7% in the LDD patients."
    The Results section of the abstract should also reflect this change and read: "In addition, a significantly smaller number of controls was heterozygotes for this allele".


  • * Drs Tilkeridis and Bei have contributed equally to this work and are thus sharing first authorship. Dr Tilkeridis is currently at the Department of Orthopaedics, Demokrition University, Thrace, Greece; Dr Garantziotis is currently at Department of Medicine at Duke University Medical Center, Durham, North Carolina 27710, USA.

  • Competing interests: none declared