Identification of three new single nucleotide polymorphisms in the human tumor necrosis factor‐α gene promoter

Abstract
We have identified three new human tumor necrosis factor‐α (TNF‐α) promoter polymorphisms with single nucleotide (nt) substitutions at ‐862, ‐856, and ‐574 nt relative to the TNF‐α transcription start site. The ‐862 and ‐856 nt TNF‐α promoter polymorphisms occur with high frequency in Caucasian and Cambodian individuals and are each non‐ran‐domly associated with three extended HLA haplotypes. This study, in which 61 independent TNF‐α promoters were analyzed spanning from ‐977 to +93 nt relative to the TNF‐α mRNA cap site, establishes a new canonical TNF‐α promoter sequence. Furthermore, we show that none of the three novel polymorphisms at ‐862, ‐856 and ‐574 nt or polymorphisms previously described at positions ‐238, ‐308 and +70 have an effect upon TNF‐α gene expression in activated lymphocytes. Thus, these TNF‐α promoter polymorphisms likely serve as markers for neighboring genes encoding HLA or other undefined molecules in the MHC that may influence disease susceptibility.

This publication has 36 references indexed in Scilit: