GENETIC-POLYMORPHISM OF HUMAN INTERLEUKIN-1-ALPHA

Interleukin-1alpha (IL-1alpha) has been implicated in the pathogenesis of infectious, autoimmune and inflammatory diseases. There is, howeve r, very little information on the cis-acting sequences involved in IL- 1alpha regulation or whether there is any variation in the structure o f the gene. It is known that intron 6 of IL-1alpha shows a 5 x 46 bp t andem repeat in the genomic sequence.We have studied this region of th e gene. Amplification by polymerase chain reaction showed different si zed products from different individuals, most being of higher molecula r weight than the expected size of 620 bp. Sequencing demonstrated tha t the polymorphism was due to a variable number of repeats of the 46 b p sequence.This was confirmed by restriction fragment length analysis of genomic DNA. Altogether, 72 unrelated individuals were tested and 6 alleles ranging from 5 to 18 repeats were found, the most frequent al lele (62%) containing 9 repeats. This polymorphism may be of interest in gene function, since each repeat contains three potential binding s ites for transcriptional factors: an SP1 site, a viral enhancer elemen t and a glucocorticoid-responsive element. The latter, at least, demon strates site-specific protein binding by electromobility shift assay. The functional significance of the polymorphism and its allelic freque ncy in inflammatory and autoimmune diseases are currently under invest igation.