NOVEL INTERLEUKIN-1 RECEPTOR ANTAGONIST EXON POLYMORPHISMS AND THEIR USE IN ALLELE-SPECIFIC MESSENGER-RNA ASSESSMENT

A variable number of tandem repeats (VNTR) polymorphism has been descr ibed in intron 2 of the interleukin-1 receptor antagonist gene. Allele 2 of this polymorphism is associated with many chronic inflammatory d iseases. Using direct sequencing of polymerase chain reaction products from individuals of known genotype for the VNTR, we have identified f our single base change polymorphisms in exons 1(ic) and 2 and one upst ream of exon 1(ic), all of which are probably in linkage disequilibriu m with the intron 2 VNTR. The exonic polymorphisms do not alter the en coded amino acid sequence. Using the exon 2 polymorphism as a marker f or the intron 2 disease-associated allele, we have been able to analys e allele-specific mRNA in heterozygotic keratinocyte cell lines. The d isease-associated allele shows no difference from other alleles in thi s cell type with respect to mRNA accumulation.