Evaluation of Common Variants in Matrix Metalloproteinase-9 Gene with Lumbar Disc Herniation in Han Chinese Population.

Abstract

Lumbar disc herniation (LDH) is a common and frequent orthopedic disease with strong genetic determinants. The disruption of the intervertebral disc extracellular matrix has been found to play a key role in the development of LDH, suggesting that abnormal matrix metalloproteinases (MMPs) may promote the degradation of the disc matrix. MMP-9, an important member of the MMP family, is a good candidate for the LDH susceptibility gene. The present study aimed to investigate the association of common variants in the MMP-9 gene with the risk, severity, and clinical characteristic variables of LDH. Fourteen tag single nucleotide polymorphisms (SNPs) entirely covering the region of the MMP-9 gene were analyzed in a sample of 845 patients and 1751 healthy controls. The SNP rs17576 was found to be significantly associated with susceptibility to LDH (OR = 0.77, p = 0.0002), which was also confirmed by haplotype-based analyses (rs79845319-rs17576-rs45437897, global p < 0.001). Our results indicated that the A allele of rs17576 reduced the risk of LDH by ∼23% on average. Furthermore, the G allele of rs17576 was found to correlate with more severe grades of disc degeneration. Our results provide additional evidence supporting an important role of the MMP-9 gene in the pathogenesis of LDH.