The purpose of this study was to investigate the possible relationship between matrix metalloproteinase-3 (MMP-3) promoter 5A/6A polymorphism and intervertebral disc (IVD) degeneration in the older generation. One of the important steps in IVD degeneration is disc matrix degradation by matrix degrading enzymes such as MMPs. MMP-3 is one of the potent proteoglycan degrading enzymes and has been suggested to play an important role in IVD degradation. A common 5A/6A polymorphism in the promoter region of the human MMP-3 gene has been identified. This polymorphism was reported to be involved in the regulation of MMP-3 gene expression (the 5A allele has 2-fold higher promoter activity than 6A). We now hypothesize that IVD degeneration is associated with MMP-3 promoter 5A/6A polymorphism. Forty-nine elderly Japanese volunteers (mean age 74.3 years, range 64–94 years) were studied. Each lumbar disc was graded according to the radiographic classification system of IVD degeneration described by Kellgren and Lawrence. The 5A/6A polymorphism was determined with both single strand conformation polymorphism (SSCP) and polymerase chain reaction with allele-specific primers (AS-PCR). Two subjects (4%) with 5A5A genotype, 16 (33%) with 5A6A, and 31 (63%) with 6A6A were observed. Genotype was totally independent of age and sex. There was a significantly larger number of IVDs graded 2 and higher in the 5A/5A+5A/6A than in the 6A/6A (p<
0.05). The degenerative scores of lumber discs were also distributed more highly in the 5A/5A+5A/6A than in the 6A/6A (p=0.0029). Many environmental factors have been reported to accelerate IVD degeneration. Recently, genetic factors have also been highlighted as possible risk factors. The 5A allele of the human MMP-3 promoter is a possible risk factor for acceleration of IVD degeneration in people aged over 64 years old. We conclude that MMP-3 plays a key role in the degeneration of IVD in the older generation.
It has been suggested that matrix metalloproteinase-3 (MMP-3, stromelysin-1) has an important role in the degeneration of intervertebral discs (IVDs). A human MMP-3 promoter 5A/6A polymorphism was reported to be involved in the regulation of MMP-3 gene expression. We suggest that IVD degeneration is associated with 5A/6A polymorphism. We studied 54 young and 49 elderly Japanese subjects. Degeneration of the lumbar discs was graded using MRI in the younger group and by radiography in the elderly. 5A/6A polymorphism was determined by polymerase-chain reaction-based assays. We found that the 5A5A and 5A6A genotype in the elderly was associated with a significantly larger number of degenerative IVDs than the 6A6A (p <
0.05), but there was no significant difference in the young. In the elderly, the IVD degenerative scores were also distributed more highly in the 5A5A and 5A6A genotypes (p = 0.0029). Our findings indicate that the 5A allele is a possible risk factor for the acceleration of degenerative changes in the lumbar disc in the elderly.
