Radiographic progression of lumbar spine disc degeneration is influenced by variation at inflammatory genes: a candidate SNP association study in the Chingford cohort.
METHODS
A candidate gene association study in a longitudinal cohort.


OBJECTIVE
To investigate the association between polymorphisms at 25 candidate genes and progression of individual radiographic features of lumbar disc degeneration (LDD).


BACKGROUND
LDD is characterized radiographically by the presence of osteophytes and disc space narrowing and is known to have a genetic component. Because of the high prevalence of radiographic features, progression may be a more useful phenotype clinically to study than prevalence itself.


METHODS
We tested the effect on radiographic progression of LDD of polymorphisms in 25 genes, 24 of which had been previously tested with regards to knee osteoarthritis. The progression traits used were the change in radiographic grade over 9 years in osteophytes, disc space narrowing, and summary Kellgren-Lawrence grade. Lumbar spine radiographs (L1-L5) at baseline and at follow-up were read for 720 women genotyped at the 25 genes participating in the Chingford study.


RESULTS
Polymorphisms in MMP3, TIMP1, and COX2, which encode molecules involved in inflammatory pathways, were associated with radiographic progression of LDD. The strongest associations observed (statistically significant after correcting for multiple comparisons) were between COX2 and change in osteophyte grade (P < 0.001) and Kellgren-Lawrence grade (P < 2 x 10(-5)), and between the genes for vitamin D receptor (P < 0.002) and a thrombospondin (THSD2) (P < 0.002) and change in osteophyte grade.


CONCLUSIONS
Our results suggest a role for genes regulating inflammatory pathways in the radiographic progression of spine degeneration. This could prove a fruitful area for future therapeutics for the spine and other joints.
Valdes
Ana M
AM
Twin Research & Genetic Epidemiology Unit, St. Thomas Hospital, London, UK.
Hassett
Geraldine
G
Hart
Deborah J
DJ
Spector
Tim D
TD
D051546:Cyclooxygenase 2 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007405:Intervertebral Disc Displacement / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D008137:Longitudinal Studies; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011859:Radiography; D013128:Spinal Osteophytosis / Q000000981:diagnostic imaging / Q000235:genetics; D019699:Thrombospondins / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
D008565:Membrane Proteins; D019699:Thrombospondins; D019715:Tissue Inhibitor of Metalloproteinase-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019278:Matrix Metalloproteinase 3