IDENTIFICATION OF AN 18 BASEPAIR DELETION IN THE PAI-1 GENE PROMOTER REGION IN A FAMILY WITH THROMBOTIC DISEASE

A 18 basepair (bp) deletion has been found in the plasminogen activato r inhibitor (PAI-1) gene promoter region in a patient who developed de ep vein thrombosis during pregnancy. The deletion corresponds to nucle otides -589 to -606 and is linked to the earlier described polymorphic 4G allele at position -675. The patient had a positive family history of thrombosis. Five out of eleven family members were found to have s uffered from thrombosis. Of these five, four were heterozygous for the deletion variant. In addition, two individuals without thrombosis als o had the same deletion. At present, it is not possible to either esta blish or exclude an association between this 18 bp deletion and thromb otic disease. The plasma PAI-I levels do not seem to be affected by th e deleted DNA sequence. The DNA sequence in this region is not homolog ous to the binding sites of known transcription factors. The presence of direct repeats within this region is interesting and may indicate a possible mechanism for the occurrence of the deletion involving 'slip page' of the DNA polymerase during replication.