The functional MMP-9 microsatellite marker is not associated with episodic memory in humans

Abstract

One candidate gene for involvement in memory function is matrix metalloproteinase 9 (MMP-9). It is synthesized in neurons of the human hippocampus (Backstrom et al., 1996), and plays an important role in synaptic plasticity and hippocampal-dependent learning (Meighan et al., 2006). MMP-9 has a functional repeat polymorphism (CA)n in its promoter sequence (Shimajiri et al., 1999) and mice that lack the gene exhibit impairments in long-term potentiation and hippocampal-dependent associative learning. As this polymorphism is functional, and MMP-9 is involved in hippocampal memory and learning, we hypothesized that this polymorphism modulates human cognitive function. To test this, we genotyped the MMP-9 microsatellite in 449 normal Han Chinese participants who had taken a set of cognitive tests including episodic memory. No significant association between the polymorphic alleles or genotype and memory was detected. This is the first study to test the functional MMP-9 microsatellite polymorphism for association with memory in humans. The results do not support an influence of this polymorphism on memory function, in the population studied. The absence of a significant effect could be explained by the lack of short (low activity) alleles in our Asian sample. Another explanation for the lack of association could be that complex characteristics, such as memory, and MMP-9 enzyme activity do not have a linear correlation, as MMPs have both detrimental and beneficial effects on the central nervous system. Upregulation of MMP-9 has been reported in various neurological conditions and brain injury, suggesting neurotoxicity; however, a beneficial effect of MMP-9 on the repair process, such as axonal regeneration and myelination, has also been demonstrated (Yong, 2005). Apparently, our findings reflect the difficulty in associating biochemical alterations with complex psychological phenomena. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.