The Mal/TIRAP S180L and TLR4 G299D polymorphisms are not associated with susceptibility to, or severity of, rheumatoid arthritis

Background:Toll-like receptors (TLRs), including TLR4, have been implicated in the pathogenesis of rheumatoid arthritis (RA). Signalling by these receptors involves interactions with intracellular proteins, including the MyD88 adapter-like (Mal) protein. Recently, a polymorphism (Mal S180L) has been described which contributes to susceptibility to common infectious diseases and inhibits proinflammatory cytokine production. A non-synonymous variant in the extracellular domain of TLR4 (G299D) has been shown to interrupt TLR4-mediated signalling, resulting in endotoxin hyporesponsiveness.Objective:To investigate the role of TLR4 G299D and Mal S180L variants in RA.Methods:A total of 964 Caucasians with RA and 965 controls were genotyped. Deviation from Hardy–Weinberg equilibrium was tested for each single nucleotide polymorphism in cases and controls separately using a χ2 test with a threshold of p