Association of an EAAT2 polymorphism with higher glutamate concentration in relapsing multiple sclerosis.

Glutamate excitotoxicity contributes to oligodendrocyte and tissue damage in multiple sclerosis (MS). Here, we have examined if glutamate homeostasis is altered in plasma from MS patients. We initially observed that plasma glutamate levels are elevated in MS patients as compared to control subjects. In addition, we have studied the presence of a polymorphism sited in the promoter of the glutamate transporter EAAT2 whose mutant genotype results in lower transporter expression. We found that the polymorphism is not associated with the risk to develop MS. However, it is associated with higher glutamate plasma levels during the course of a relapse. These findings suggest that glutamate homeostasis is compromised in MS and that carrying this mutation may contribute to this alteration in relapsing MS.