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

Nyati, Kishan Kumar; Prasad, Kashi Nath; Verma, Avantika; Singh, Aloukick Kumar; Rizwan, Arshi; Sinha, Sushmita; Paliwal, Vimal Kumar; Pradhan, Sunil

doi:10.1016/j.jneuroim.2009.10.018

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Volume 218, Issue 1 , Pages 116-119, 25 January 2010

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

Kishan Kumar Nyati
- Department of Microbiology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow-226 014, Uttar Pradesh, India
Kashi Nath Prasad
- Department of Microbiology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow-226 014, Uttar Pradesh, India
- Corresponding author. Tel.: +91 522 2668700 2265; fax: +91 522 2668100, +91 522 2668017.
Avantika Verma
- Department of Microbiology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow-226 014, Uttar Pradesh, India
Aloukick Kumar Singh
- Department of Microbiology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow-226 014, Uttar Pradesh, India
Arshi Rizwan
- Department of Microbiology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow-226 014, Uttar Pradesh, India
Sushmita Sinha
- Department of Microbiology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Lucknow-226 014, Uttar Pradesh, India
Vimal Kumar Paliwal
- Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
Sunil Pradhan
- Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

Received 25 May 2009; received in revised form 21 October 2009; accepted 23 October 2009. published online 16 November 2009.

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.

Keywords: Guillain-Barré syndrome, TLR4 polymorphism, Campylobacter jejuni, Lipopolysaccharide