Tumor necrosis factor–α polymorphisms and expression in Guillain–Barré syndrome

Abstract

Tumor necrosis factor–α (TNF-α) polymorphisms with increased expression is associated with many autoimmune and inflammatory diseases. Possible role of TNF-α polymorphism in the pathogenesis of Guillain–Barré syndrome (GBS) largely remains unknown. We investigated polymorphisms in the promoter region of TNF-α gene and its expression in GBS patients and healthy controls. TNF-α (−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-α level in serum by ELISA was determined in 60 patients and an equal number of controls. Prevalence of TNF-α −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-α −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-α level in serum. TNF-α −308 G > A and −857 C>T (only T/T) polymorphisms with increased TNF-α level may predict susceptibility to axonal subtypes of GBS.