Tumor necrosis factor-alpha polymorphisms and expression in Guillain-Barré syndrome.

Tumor necrosis factor-alpha (TNF-alpha) polymorphisms with increased expression is associated with many autoimmune and inflammatory diseases. Possible role of TNF-alpha polymorphism in the pathogenesis of Guillain-Barré syndrome (GBS) largely remains unknown. We investigated polymorphisms in the promoter region of TNF-alpha gene and its expression in GBS patients and healthy controls. TNF-alpha (-308 G>A, -857 C>T, and -863 C>A) polymorphisms in 140 GBS patients and 206 healthy controls were studied using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-PCR. TNF-alpha level in serum by ELISA was determined in 60 patients and an equal number of controls. Prevalence of TNF-alpha -308 G > A polymorphic A allele was associated with increased risk of GBS (p < 0.001; OR = 2.58, 95% CI = 1.61-4.14). Heterozygous genotype (G/A) had an association with acute motor axonal neuropathy (p < 0.001; OR = 4.23, 95% CI = 2.00-8.95) and variant genotype A/A with both axonal subtypes, acute motor axonal neuropathy (p = 0.015, OR = 7.00, 95% CI = 1.46-33.57) and acute motor sensory axonal neuropathy (p = 0.017; OR = 7.73, 95% CI = 1.44-41.37). Variant genotype T/T of TNF-alpha -857 C>T polymorphism was also significantly associated with acute motor axonal neuropathy (p = 0.034; OR = 3.93, 95% CI = 1.11-13.91). Patients with A and T alleles had higher TNF-alpha level in serum. TNF-alpha -308 G > A and -857 C>T (only T/T) polymorphisms with increased TNF-alpha level may predict susceptibility to axonal subtypes of GBS. Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.