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.
Kroner
A
A
Clinical Research Group for Multiple Sclerosis and Neuroimmunology, Department of Neurology, Bayerische Julius-Maximilians Universität Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany.
Vogel
F
F
Kolb-Mäurer
A
A
Kruse
N
N
Toyka
K V
KV
Hemmer
B
B
Rieckmann
P
P
Mäurer
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001224:Aspartic Acid / Q000235:genetics*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D005858:Germany; D005998:Glycine / Q000235:genetics*; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013912:Threonine / Q000235:genetics; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D016207:Cytokines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D007532:Isoleucine; D013912:Threonine; D001224:Aspartic Acid; D005998:Glycine