Torres-Merino S, Moreno-Sandoval HN, del Rocio Thompson-Bonilla M, Gonzalez-Barrios JA, Leon-Chavez BA and Martinez-Fong D
Background: Recently it has been shown an increase in the interleukin 1 beta and nitrite levels in cerebrospinal fluid as a primary response of the immature brain to oxygen deprivation in newborns that suffered perinatal asphyxia, 30% to 40% of these patients later develop neurological abnormalities incluiding cerebral palsy. Formerly was shown that an increased enzyme activity of NOS2 is responsible for the increase in nitrite levels in cerebrospinal fluid. The NOS2A gene has a polymorphic microsatellite (CCTTT)n located at -2.6 Kb from the gene promoter. The expansion of this microsatellite to 13 or 14 repeats increases transcription of the NOS2A gene and triples the nitric oxide level under hypoglycemia and hypoxia conditions. The study aim was shown that the expansion of -2.6 Kb CCTTT microsatellite in the NOS2 gene promoter, constitutes a risk factor for developing cerebral palsy in newborns that suffered perinatal asphyxia Methods: Genomic DNAs purified from peripheral leukocytes of 48 ICP patients and 57 healthy children, the (CCTTT)n microsatellite expansion were amplified by PCR, purified from agarosa gel in micro-column method and sequenced using genomelab methods development kit cycle sequencing dye terminator in an automated CEQ8000 sequencer. Results: The presence of a 14-repeat is significantly associated with infant cerebral palsy (Fisher P value=0.0122). Multivariate analysis adjusted for age and sex confirmed the association with an increased risk of developing infant cerebral palsy (odds ratio, 1.78; 95% confidence interval, 1.150-2.752; P=0.01). Conclusions: Our findings suggest that an expansion to 14 repeats of the CCTTT microsatellite plays a key role in the development of cerebral palsy in children that suffered perinatal asphyxia.
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