GDF5 SNP rs143383 is associated with lumbar disc disease in northern European women.

OBJECTIVE: Lumbar degenerative disc disease (LDD) is a serious social and medical problem which has been shown to be highly heritable. It has similarities with peripheral joint osteoarthritis (OA) both in terms of epidemiology and pathological processes. A few known genetic variants have been identified using a candidate gene approach, but many more are thought to exist. GDF5 is a gene whose variants have been shown to play a role in skeletal height as well as predisposing to peripheral joint OA. In vitro the gene product, growth and differentiation factor 5, has been shown to promote growth and repair of animal disc. Thus the GDF5 gene, we postulated, might play a role in LDD. METHODS: We investigated whether the 5' upstream SNP variant rs143383 was associated with LDD, determined using plain film and MRI to ascertain disc space narrowing and osteophytes, in 5 population cohorts from Northern Europe. RESULTS: Association with the SNP rs143383 was identified in women, with the same risk allele as in knee and hip OA with OR= 1.72 (95% confidence intervals 1.15-2.57, p=0.008). CONCLUSION: Using 5 population cohorts from Northern Europe we have identified a variant in the gene GDF5 as a risk factor for LDD in women. Many more such variants are predicted to exist, but this result throws the spotlight onto the growth and differentiation cellular pathway as a possible route to understanding better the process behind degenerative disc disease.