The cytokine TNF-alpha. Genetics and suitability for prenatal risks assessment

The tumor necrosis factor (TNF-alpha) is a cytokine known as a mediator of inflammation and immunity. The genes coding the tumor necrosis factors alpha and beta are considered part of class III major histocompatability complex. The 2 involved genes have been mapped to chromosome 6. Certain mutations in the TNF-alpha gene are believed to be causative for increased production of the cytokine. In this respect, the most common variant is the TNF2 allele, a single nucleotide substitution of guanine by adenine at position -308 relative to the promoter transcription site of the gene. Elevated production of TNF-alpha has been found to be associated with several infectious diseases including malaria. Elevated levels of TNF-alpha have also been observed to associate with increased risk of preterm delivery, chorioamnionitis and fetal morbidity including encephalopathy. The present article reviews the genetics of the cytokine TNF-alpha and discusses its suitability as a candidate marker for assessment of increased risk of preterm delivery and fetal morbidity.