All polymorphisms studied in this paper [PMID: 18180278] , total : 2 polymorphisms

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

Abstract : 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 chi(2) test with a threshold of p<0.05. The odd ratios were calculated with asymptotic 95% confidence intervals, and p values <0.05 were considered significant. Epistasis was assessed using both stratified analysis and the linkage disequilibrium-based statistic. RESULTS: Mal S180L genotypes were similar in cases and controls (OR = 0.9, 95% CI 0.7 to 1.0, p = 0.2). Similarly, no difference for TLR4 G299D genotypes was seen (OR = 1.7, 95% CI 0.3 to 11.1, p = 0.5). No association with either rheumatoid factor or anti-cyclic citrullinated peptide status or with radiological damage was detected. Finally, no evidence of epistasis was detected between Mal S180L and TLR4 G299D and RA susceptibility. CONCLUSIONS: The Mal S180L and TLR4 G299D polymorphisms do not contribute to RA susceptibility or severity either individually or in combination.

Author : Sheedy FJ,Marinou I,O'Neill LA,Wilson AG,

Source : Ann Rheum Dis. 2008 Sep;67(9):1328-31. doi: 10.1136/ard.2007.083337. Epub 2008 Jan 7.

No.	Polymorphism name	Gene Symbol	Entrez Gene ID
1	NA	TIRAP	114609
2	rs4986790	TLR4	7099