Abstract
Introduction
A significant association between non-specific low back pain and Modic changes (MC) have been described. We hypothesied that a single nucleotide polymorphisms(SNP) may be involved in matrix and bone metabolism associated changes with modic changes. The present study purports to evaluate the prevalence of MC and the role of genetic polymorphisms in 40 candidate genes (including 71 SNPs).
Methods
The study was a cross sectional study performed on 809 patients irrespective of back pain status. Assessment was performed with MRI evaluation and genetic association analysis of 71 SNPs belonging to 40 genes. Inclusion criteria for patients were both sexes, age of 18 to 70 years, no evidence of other spinal diseases, previous surgery & trauma. The MRI included T1 and T2 sagittal sections of the lumbar spine. The presence and type of Modic changes & the genetic association analysis of 71 SNPs was made with reference to the presence or absence of Modic Changes. Genotyping of SNPs was performed using the Sequenome® platform.
Results
809 individuals of mean age 36.7 ± 10.8 years were studied. Based on the presence of MC, the group was divided into 702 controls and 107 cases. 64 patients had single level MC (7.9%), 32 had double level (3.9%), 5 had three and four level MC (0.6%) and one had multi-level MC. Modic changes were identified in 251 of the 1070 endplates (EP). MC was more commonly situated in the lower EP (149, 59.4%) than in the upper EP (102, 40.6%). L4–5 EP were the most commonly affected level (n = 77, 30.7%) followed by L5-S1 (26.3%), L3–4 (23.9%), L2–3 (12.4%) and L1–2 (6.8%). Type 2 MC was the most commonly observed pattern (n = 206, 82%), followed by Type 1 (n = 27, 10.8%) and Type 3 (n = 18, 7.2%). Mirroring endplate MC was observed in 75 discs (29.8%) among the total 535 discs. SNPs of Vitamin D receptor gene (VDR) and Matrix Metallo proteinase (MMP20) (p = 0.03) were significantly associated with MC. SNP of cyclo-oxygenase gene(COX2) and Insulin Growth Factor Receptor(IGF1R) (p = 0.03) were significantly associated with Type 2 MC.
Conclusion
The study identifies genetic polymorphisms of VDR, MMP 20, COX 2 and IGF1R to be significantly associated with MC and have not been reported previously. Understanding the etiopathogenetic of Modic changes would help us to plan preventive and therapeutic strategies