Abstract
Introduction
Although the exact mechanisms that lead to degenerative disc disease (DDD) are not well understood, a significant genetic influence has been found. Focusing on DDD that occurs in young adults can be valuable in determining the exact role of genetic predisposition to DD. The present study was undertaken to assess the association between single nucleotide polymorphisms (SNPs) of candidate genes in a cohort of young Indian adults.
Materials and Methods
We selected young patients (age < 40 years) with lumbar disc degeneration and evaluated them with MRI and genetic association studies for 58 SNPs of 35 candidate genes. Disc degeneration of individual discs of lumbar spine from L1 to S1 was quantified by Pfirrmann grading in MRI images (1.5 T). The subjects were stratified into three groups based on a total degenerative disc score (TDDS). TDDS was developed by adding the individual scores of Pfirrmann grading of all the five lumbar discs. Based on the TDDS, the severity of DDD among the subjects was classified as mild (TDDS < 10), moderate (TDDS of 10-15), and severe (TDDS > 15). The patients were classified into three groups so that the extreme confounding patients in the mild and severe TDDS groups will automatically fall into the moderate TDDS group. For the final association analysis, only the results of mild (the unaffected, control group) and severe TDDS groups (affected, case group) were compared and analyzed.
Results
The study population comprised 580 subjects including 308 patients with mild TDDS, 211 patients with moderate TDDS, and 61 patients with severe TDDS. There was no significant difference in the gender difference and the mean age of the both groups. Three of the 35 candidate genes showed significant association with severe TDDS. SNPs, viz., rs1940044 of MMP (matrix metalloproteinase 7), rs2300496 SNP and rs3213718 SNPs of CALM1 (calmodulin), and rs5277 of COX 2 (cyclooxygenase) were found to be significantly associated with severe TDDS. Among the previously reported candidate genes, our analysis in the young Indian population had revealed that SNPs of COL 9, SKT, CHST 3, CILP, IGFR, SOXp, BMP, MMP 2-12, ADH2, IL1RN, AGC 1, ADAMTS5, NGFB, GLI, HHIP, TAC1, and IL1B were not significantly associated with severe TDDS.
Association analysis of SNPs with Pfirrmann grading (less than 40 years of age; controls with TDDS of < 10 and cases with score of > 15)
| S. No. | Chromosome | Gene | SNP | p-Value |
|---|---|---|---|---|
| aSignificant at 1% level. | ||||
| bSignificant at 5% level. | ||||
| 1 | 11 | MMP7 | rs1940044 | 0.001416a |
| 2 | 14 | CALM1 (calmodulin) | rs2300496 | 0.007355a |
| 3 | 14 | CALM1 (calmodulin) | rs3213718 | 0.008906a |
| 4 | 1 | COX2 | rs5277 | 0.04124b |
Conclusion
This is the first of its kind in studying the genetic aspects of disc degeneration in the young adults. The study identifies specific SNP associations of three genes (MMP 7, CALM 1, and COX2) in young adults with severe lumbar disc degeneration. Genes involved in matrix degradation (MMP), intracellular signaling (CALM), and inflammation (COX 2) were associated with early disc degeneration indicating that DDD is a complex disease with an intricate interplay of multiple genetic polymorphisms.
None declared