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TNFalpha genotypes and risk for cerebral palsy in preterm and term infants

BACKGROUND. Cerebral palsy is a nonprogressive motor disorder caused by white matter damage in the developing brain. Activation of the cytokine network by a variety of insults (infection and/or hypoxia-ischemia) and elevated levels of proinflammatory cytokines can cause white matter brain damage as well as the development of CP. Recent data suggest a significant role of TNFα in the pathophysiology of perinatal brain injury. The aim of our study was to investigate the influence of TNFα promoter SNPs on susceptibility to CP in preterm and term neonates. METHODS. We analyzed 94 CP patients and control group of 118 unrelated children with comparable gestational age and sex distribution. Real-time PCR SNP analysis of TNFα SNPs was performed using predeveloped TaqMan SNP genotyping assay reagents. RESULTS. Statistically significant association between TNFα -1031 T/C high expression genotypes (TC and CC) and risk of CP was observed (OR 2.1811 (1.2075-3.9396), p=0.0097). Statistically significant association was also found between TNFα -1031C high expression allele and risk of CP (OR 1.9909 (1.1831-3.3501), p=0.0095). Statistically significant association between TNFα -1031 T/C high expression genotypes (TC and CC) and risk of CP was observed in term children (OR 4.7475 (1.5576-14.4696), p=0.0062) but not in preterm infants. Statistically significant association was also found between TNFα -1031C high expression allele and risk of CP in term children (OR 3.0952 (1.2124-7.9020), p=0.0181). CONCLUSION. Our results suggest a role of TNFα -1031 T/C gene polymorphism as modifying factor for development of CP in term, but not in preterm infants.

cerebral palsy; tumor necrosis factor alpha; cytokine polymorphisms

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