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

Objectives Febrile seizure is a neuroinflammatory disease involving fever induced seizures affecting children in the early stages of life. TNF alpha is a pro-inflammatory cytokine reported to be elevated in FS. Specific promoter variants of TNF alpha could be associated with its elevated cytokine expression and susceptibility to FS. The present study analyzed the association of specific TNF alpha variants, including TNF alpha-238 G/A (a genetic variant; G: Guanine, A: Adenine) (rs361525), TNF alpha-308 G/A (rs1800629), and TNF alpha-376 G/A (rs1800750) promoter polymorphisms, with FS susceptibility, and TNF alpha serum levels in an Iranian population.This study revealed that AGA (a genetic sequence; G: Guanine, A: Adenine) (-238/-308/-376) haplotype with the highest frequency in controls was associated with a decreased risk of FS, while GAA (a genetic sequence; G: Guanine, A: Adenine) (-238/-308/-376) carriers were more susceptible to FS. Conclusion The current study suggested that TNF alpha gene promoter variants at rs361525, rs1800629, and rs1800750 could be associated with the susceptibility to FS and altered serum levels of TNF alpha.