Association of TLR4 Asp299Gly and Thr399Ile polymorphisms with Guillain-Barré syndrome in Northern Indian population

Abstract

Molecular mimicry between Campylobacter jejuni lipopolysaccharide and host gangliosides induces an immune response leading to axonal damage and Guillain-Barré syndrome (GBS). TLR polymorphisms are associated with many autoimmune diseases. The role of the TLR4 gene in GBS susceptibility largely remains unknown. We investigated TLR4 polymorphism in GBS. One hundred and twenty GBS patients and 150 healthy controls were included. TLR4 (Asp299Gly and Thr399Ile) genes were studied by PCR-RFLP. TLR4 (Asp299Gly) polymorphism was significantly associated with GBS ( p, 0.045; OR, 8.75; 95% CI, 1.05–72.88); only acute motor axonal neuropathy (AMAN) was associated with Gly299Gly homozygote ( p, 0.027; OR, 12.40; 95% CI, 1.33–115.77) and Thr399Ile ( p, 0.019; OR, 3.42; 95% CI, 1.22–9.54) heterozygote, and TLR4–399Ile allele ( p, 0.045; OR, 2.63; 95% CI, 1.02–6.75) compared to controls. In conclusion, TLR4 (Asp299Gly) polymorphism is associated with an increased susceptibility to GBS. Besides Asp299Gly, AMAN subtype is also associated with Thr399Ile polymorphism.