An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles.

TLDR

The TNF‑α gene resides in the class III region of the MHC, between class II and class I loci. The authors used PCR and single‑stranded conformational polymorphism to analyze TNF‑α promoter polymorphism frequencies in HLA‑typed subjects. A novel biallelic promoter polymorphism of TNF‑α was identified and found to be strongly associated with HLA‑A1, B8, and DR3, suggesting a potential role in the autoimmune susceptibility of this haplotype.

Abstract

The tumor necrosis factor (TNF) alpha gene lies within the class III region of the major histocompatibility complex (MHC), telomeric to the class II and centromeric to the class I region. We have recently described the first polymorphism within the human TNF-alpha locus. This is biallelic and lies within the promoter region. Frequency analysis of the TNF-alpha polymorphism, using the polymerase chain reaction and single-stranded conformational polymorphism, in HLA-typed individuals, reveals a very strong association between the uncommon TNF allele and HLA A1, B8, and DR3 alleles. This is the first association between TNF-alpha and other MHC alleles and raises the possibility that the uncommon TNF-alpha allele may contribute to the many autoimmune associations of the A1,B8,DR3 haplotype.