Tumor Necrosis Factor Alpha (TNFα) Gene Promoter Polymorphisms and Haplotypes are Associated with the Febrile Seizure (FS) and TNFα Serum Levels.

Abstract

Febrile seizure (FS) is a neuroinflammatory disease involving fever-induced seizures affecting children in the early stages of life. TNFα is a pro-inflammatory cytokine reported to be elevated in FS. Specific promoter variants of TNFα could be associated with its elevated cytokine expression and susceptibility to FS. The present study analyzed the association of specific TNFα variants, including TNFα -238 G/A (rs361525), TNFα -308 G/A (rs1800629), and TNFα -376 G/A (rs1800750) promoter polymorphisms, with FS susceptibility, and TNFα serum levels in an Iranian population. Sixty-eight FS patients and 136 controls were enrolled. The SSP-PCR method was utilized to analyze TNFα promoter genotypes. This research also confirmed the genotyping results by sequencing samples of ten patients and normal controls. The GG genotype of -238 SNP was associated with the increased risk of FS [OR = 12.65, 95% CI (2.83-56.60), P-value = 0.0012]. The AA genotype in the-308 region was increased in patients with FS and associated with the disease [OR = 4.62, 95% CI (1.46-14.56), P-value = 0.028]. The increased occurrence of heterozygous AG in the -376 SNP among control groups has been linked to a decreased risk of FS [OR = 0.22, 95% CI (0.11-0.43), P-value = 0.0001]. This study revealed that AGA (-238/ -308/ -376) haplotype with the highest frequency in controls was associated with a decreased risk of FS, while GAA (-238/ -308/ -376) carriers were more susceptible to FS. The current study suggested that TNFα gene promoter variants at rs361525, rs1800629, and rs1800750 could be associated with the susceptibility to FS and altered serum levels of TNFα.