Impact of the Asp299Gly polymorphism in the toll-like receptor 4 (tlr-4) gene on disease course of multiple sclerosis

In multiple sclerosis patients, infection is often associated with disease deterioration. Lipopolysaccharide (LPS) from gram-negative bacteria signals via the toll-like receptor 4 (TLR-4) pathway. Therefore, we investigated the role of an Asp299Gly mutation in the TLR-4 receptor in 890 MS patients with multiple sclerosis and 350 healthy controls. No association of different genotypes with MS susceptibility, MS subtypes, or disease severity was found. In vitro LPS stimulation studies showed a significantly lower proliferation of PBMCs from donors heterozygous for the Asp299Gly mutation in comparison to PBMCs from individuals with the wild-type genotype (p = 0.01). However, these functional changes seem not to have any impact on the clinical presentation of MS patients with different TLR-4 genotypes.