Study design: A cross-sectional genotype-phenotype evaluation.
Objective: To evaluate the genetic background to Modic changes in an occupational cohort.
Summary of background data: Modic changes are vertebral endplate changes visible in magnetic resonance imaging. Twin studies suggest that intervertebral disc degeneration may be primarily explained by genetic factors, but no data exist on genetic factors of Modic changes.
Methods: Thirteen variations in 8 genes (COL9A2, COL9A3, COL11A2, IL1A, IL1B, IL6, MMP3, and VDR) were genotyped in an occupational cohort of 159 male train engineers and 69 male paper mill workers. All the subjects were scanned by magnetic resonance imaging and evaluated for Modic changes.
Results: Out of the 228 subjects, 128 (56%) were found to have Modic changes at one or more disc levels, exclusively of type I in 15%, of type II in 32%, and of both type I and type II in 10%. None of the single nucleotide polymorphisms was significantly associated with Modic changes when analyzed independently, but when gene-gene interactions were evaluated, interleukin-1A (IL1A) and matrix metalloproteinase-3 (MMP3) polymorphisms together were associated with type II Modic changes (OR = 3.2, 95% CI = 1.2-8.5; P = 0.038), as was the IL1 gene cluster together with the MMP3 polymorphism (OR = 8.14, 95% CI = 1.72-38.44; P = 0.008).
Discussion: This is the first study evaluating the role of genetic factors in relation to Modic changes. Genetic variations in the IL1 cluster and the MMP3 gene together were found to be significantly associated with type II Modic changes.