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

Abstract

The tumor necrosis factor (TNF) α 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-α locus. This is biallelic and lies within the promoter region. Frequency analysis of the TNF-α 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-α and other MHC alleles and raises the possibility that the uncommon TNF-α allele may contribute to the many autoimmune associations of the A1,B8,DR3 haplotype.