Study finds MMP-9 gene variant affects MS risk

Matrix metalloprotease 9 (MMP-9) is a protease (a protein that splits other proteins) that has been implicated in the pathogenesis of MS. Experimental evidence suggests that it may play a role in activities such as the breakdown of the blood-brain barrier and the degradation of myelin. Moreover, people with MS have been found to have higher levels of MMP-9 in their blood than controls. Scientists looking for the source of this difference recently investigated whether variants in the MMP-9 gene are distributed differently between MS subjects and controls. They focused on a variable length polymorphism in the promoter region of the gene that appears to influence gene expression -- variants that have more repeated CA (cytosine–adenine) units are associated with higher levels of MMP-9 production.

95 MS subjects and 95 controls matched for age, sex and ethnic origin were recruited for the study. All subjects were from Trieste, Italy; most were of Italian origin but a minority were Slavic. The results from the genotyping showed that the lengthier polymorphisms (e.g., >= 22 repeat units) were significantly associated with both MS risk and earlier age of onset.

Two previous studies, Nelissen 2000 and Nelissen 2002, had investigated MMP-9 as a susceptibility gene for MS in the Swedish, Sardinian, and Belgian populations but did not find any association. Reasons for the discrepancies between those studies and this current one include differences in study design (such as choice of controls) as well as underlying genetic differences in the populations studied. The positive findings in this study will likely encourage further investigations of the MMP-9 variant to see if associations in other groups can be identified.