Tissue plasminogen activator gene and risk of relapsing-remitting multiple sclerosis

Zea-Sevilla M
Servicio de Neurología Hospital del Henares. Madrid. Servicio de Neurología Hospital Universitario de Canarias (Santa Cruz de Tenerife)

Abstract:

OBJETIVE:
To elucidate the relationship between the plasminogen system and relapsing-remitting multiple sclerosis (RRMS).

BACKGROUND:
Several coagulation factors have been found in the nervous system, such as tissue plasminogen activator gene (tPA). It is located in several brain areas and could be considered as a key effector in neurobiology and neuropathology, suggesting a potential role in MS inflammatory process.

METHODS:
We analyzed the polymorphic variants of tPA gene and the plasmatic levels of tPA and plasminogen in 100 RRMS patients and 131 age and sex-matched controls.

RESULTS:
The average plasmatic plasminogen levels were 102.2% in MS patients, and 107.3% in the control group (p=0.05). Average tPA mean plasmatic levels were 4.24ng/ml and 5.90ng/dl respectively (p<0.001). In the MS group, I/D genotype was found in 67%, I/I in 20%, and D/D in 13%. In the control group, the figures for the same genotypes were: 47%, 30% and 22.9%. In our population, I/D was associated with higher risk to develop MS (OR: 2.23).

CONCLUSIONS:
Plasminogen system could play a role in MS pathogenesis. Our findings may imply I/D polymorphic variants of tPA as a possible MS risk factor, suggesting that this system could generate new therapeutic targets.