AN INTRONIC POLYMORPHIC REPEAT SEQUENCE MODULATES INTERLEUKIN-1-ALPHAGENE-REGULATION

Recently, we characterized a polymorphism within IL-1 alpha intron 6 a s a variable number of a 46 bp tandem repeat (ranging from 5 to 18 rep eats). We now analyse whether this polymorphism could play a role in I L-1 alpha gene regulation. We have found that reporter gene expression driven by the IL-1 alpha promoter or a heterologous promoter was decr eased by increasing numbers of the repeat sequence corresponding to th e most frequent alleles seen in the human population. Furthermore, we showed that the transcription factor Sp1 can bind to the 46 bp sequenc e. Finally, we were unable to show a statistically-significant relatio n between in vitro IL-1 alpha production and the number of repeats alt hough there was a clear trend towards an inverse relation. Taken toget her, these results are consistent with a negative regulatory role for IL-1 alpha intron 6 repeat sequence on IL-la basal gene transcription. Copyright (C) 1996 Elsevier Science Ltd