Evaluation of the poly(ADP-ribose) polymerase gene in human stroke

Nitric oxide (NO) and its reactant product, peroxynitrite, have been implie d to mediate neuronal damage following cerebral ischemia. However, the cell ular targets of these compounds remain unclear. Studies using poly(ADP-ribo se) polymerase (PARP) inhibitors and PARP knock-out mice have recently demo nstrated that excessive activation of this nuclear enzyme plays an importan t role in NO-induced nenrotoxicity. To evaluate the relevance of this plaus ible candidate gene to human stroke, we undertook a case-control study in J apanese. Participants comprised 213 cerebral infarction cases and 374 age- and sex-matched controls. As a primary investigation, we screened polymorph ic sites of the PARP gene, and newly identified a total of four polymorphis ms in 1230-bp 5'-flanking sequence. None of them were, however, located on the known promoter components of the gene. Two bi-allelic polymorphisms sel ected and a CA-repeat polymorphism were subsequently characterized in the c ase-control study, but none were significantly associated with cerebral inf arction in the present study. Our data thus suggest that the tested PARP po lymorphisms do not principally contribute to cerebral infarction, although extensive searches would be required to clarify whether the PARP gene plays an important role in the pathogenesis of human stroke. (C) 2000 Elsevier S cience Ireland Ltd. All rights reserved.