OBJECTIVE: Single-nucleotide polymorphisms (SNPs) that alter immune function, inflammatory responses, and disease susceptibility have been identified in several genes encoding Toll-like receptors (TLRs). The TLR SNPs with the best evidence of an effect on immune function are those in @entity11709 (1805GG), @entity2938 (2258GA), and @entity20040 (1174CT). This study was undertaken to assess the frequency and functional outcomes of these polymorphisms in @entity1 with @entity3001 . METHODS: SNP frequencies and functional outcomes were assessed in 248 @entity1 with @entity3001 . Cytokine and chemokine levels were determined using multiplex assays in the serum of @entity1 with @entity8831 ( @entity8831 ), joint fluid of @entity1 with @entity625 , and supernatants of @entity2069 -stimulated peripheral blood mononuclear cells (PBMCs) from @entity1 with @entity625 . RESULTS: The frequency of the @entity11709 -1805GG polymorphism was greater in patients with antibiotic-refractory @entity625 compared with @entity1 with @entity8831 or those with antibiotic-responsive @entity625 . Early in the illness, @entity1 with @entity8831 carrying 1805GG, primarily those infected with @entity2069 16S-23S ribosomal spacer RNA intergenic type 1 (RST1) strains, had higher serum levels of interferon-y (IFNy), CXCL9, and CXCL10 and had more severe @entity281 than @entity8831 @entity1 carrying the @entity69488 polymorphism. These inflammatory responses were amplified in @entity1 with @entity625 , and the highest responses were observed in @entity1 with 1805GG in the antibiotic-refractory group who had been infected with RST1 strains. When PBMCs from @entity1 with @entity625 were stimulated with a @entity2069 RST1 strain, the 1805GG group had a significantly larger fold increase in the levels of IFNy, CCL2, CXCL9, and CXCL10 compared to the 1805TG/TT group. In contrast, the @entity2938 and @entity20040 polymorphisms did not vary in frequency or function among the groups. CONCLUSION: The @entity11709 -1805GG polymorphism in @entity2069 RST1-infected @entity1 was associated with stronger @entity1198 -like inflammatory responses, an environment that may set the stage for antibiotic-refractory @entity625 .

Association of a XXXX polymorphism with heightened @entity1198 inflammatory responses and antibiotic-refractory @entity625 .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity3001 :: ('MESH:D008193', 'Disease') :: ['Lyme disease'] @entity625 :: ('MESH:D001168', 'Disease') :: ['Lyme arthritis', 'arthritis'] @entity69488 :: ('c|SUB|TG|1805|TT', 'DNAMutation') :: ['1805TG/TT'] @entity2069 :: ('139', 'Species') :: ['B burgdorferi', 'Borrelia burgdorferi'] @entity20040 :: ('7100', 'Gene') :: ['TLR5'] @entity1198 :: ('51497', 'Gene') :: ['Th1'] @entity2938 :: ('7097', 'Gene') :: ['TLR2'] @entity8831 :: ('MESH:C538499', 'Disease') :: ['EM', 'erythema migrans'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infection'] @entity11709 :: ('7096', 'Gene') :: ['TLR1']
@entity11709 :: (7096,Gene) :: ['Toll-like receptor 1']
