The etiology of arterial ischemic stroke (AIS) in children is complex, and
different from that in adults. Although rare, stroke in children is an
important cause of mortality and morbidity. There is increasing evidence
that genetic factors, including inflammation mediators, have a role in
occurrence and outcome of stroke. We have chosen to assess the role of
polymorphism -308G/A in the promoter of tumor necrosis factor ? (TNF?) gene
and S and Z mutations in alpha 1-antitrypsin (AAT) gene in the etiology of
stroke in children. TNF? polymorphism affects plasma levels of this
proinflamatory cytokine, and this could contribute to stroke pathology. It
has been shown that increased AAT concentration may present a risk for AIS
in children. Since S and Z mutations in AAT gene reduce its levels in plasma
they could have a protective role in pediatric stroke. In this study twenty
six children with AIS and 100 unrelated individuals from Serbian general
population were investigated by PCR/RFLP for these gene variations. No
statistically significant difference was observed between patients and
general population in distribution of genotypes for -308G/A TNF?
polymorphism, so its contributory role in the etiology of stroke was not
evident in our group of patients. None of the tested AAT gene mutations were
found in patients, which is in concordance with the proposed protective role
of deficient AAT variants. AIS is a multifactorial disease, with many genes
having a modest role in its pathophysiology, so further analyses of their
combined effect are needed to elucidate genetic risk factors in the etiology
and outcome of stroke in pediatric patients.
Critical protective role of mast cell-derived tumor necrosis factor (TNF) in experimental septic peritonitis
