Perinatal asphyxia in the neonatal brain triggers a robust inflammatory response in which nitric oxide (NO) generation plays a hazardous role. Increased levels of NO can be maintained by inducible NO synthase (NOS2A) on its own or activated by IL-1beta (IL-1β) gene transcription thus potentiating brain injury after brain ischemia. We investigated whether the risk for cerebral palsy (CP) increases when an expansion of the -2.5 kb (CCTTT)n microsatellite in the NOS2A gene and a -C511T SNP of IL-1β gene promoter occur in patients after perinatal hypoxic-ischemic encephalopathy. Genomic DNA was purified from 48 patients with CP and of 57 healthy control children. IL-1β SNP genotypes were established using a qPCR and were validated by RFLP analysis. -2.5 CCTTTn microsatellite length of NOS2 was determined by sequencing. The 14 repeat long allele of the CCTTTn NOS2A microsatellite was present in 27% of CP patients vs 12.3 % of controls, showing an odds ratio (OR)=2.6531 and 95 % confidence interval (CI) = 0.9612–7.3232, P< 0.0469. The -511 TT genotype frequency showed an OR = 2.6325 (95% CI = 1.1348–6.1066), P = 0.0189. Interestingly, the haplotype CCTTT14/TT showed an OR =9.561; 95 %, CI = 1.1321–80.753; P = 0.0164.The haplotype (CCTTT)14/TT, formed by the expansion of the-2.5 kb (CCTTT)n microsatellite in the NOS2A gene promoter and the -511 C➝ T SNP of the IL-1β gene promoter, might be a useful marker to identify patients who are at high risk for developing CP after hypoxic ischemic encephalopathy.
Juan-Antonio Gonzalez-Barrios has completed his MD from CICS-IPN, his MSc, and PhD from DFBN-CINVESTAV, Mexico and postdoctoral studies from University of Florida, USA. He is the head of Genomic Medicine Laboratory, Regional Hospital “October 1st”, ISSSTE. He has published 36 papers in reputed journals and has been serving as an editorial board member of repute.