PP06.14 – 2591: Antioxidative enzyme polymorphisms and sequelae after neonatal hypoxic-ischaemic brain injury

Abstract

Objective To investigate the impact of common functional polymorphisms in antioxidative genes GPX1, SOD2 and CAT, associated with decreased capacity of defence against reactive oxygen species (ROS), in patients with epilepsy and/or cerebral palsy (CP) after perinatal hypoxic ischemic brain injury (HIBI). Hypothesis: genetically determined decreased capacity of defence against ROS may increase the risk for epilepsy and/or cerebral palsy.after perinatal hypoxic ischemic brain injury. Methods 230 consecutive patients with epilepsy and/or CP after HIBI, treated in our unite, and 95 healthy controls were included. Patients treated with therapeutic hypothermia were excluded. Patients' clinical data were collected retrospectively. Real-time PCR based methods were used to genotype GPX1 rs1050450, SOD2 rs4880 and CAT rs1001179. Statistical analysis using logistic regression was performed. Results In 214 patients with epilepsy, GPX1, SOD2 and CAT polymorphisms were not associated with the risk for epilepsy as compared to healthy controls. Similarly, the frequency distribution of GPX1, SOD2 and CAT genotypes did not differ significantly when 64 patients with epilepsy after HIBI were compared to healthy controls. Among 80 patients with HIBI, cerebral palsy was present in 51 patients. Carriers of at least one polymorphic CAT rs1001179 allele had significantly higher risk for cerebral palsy (univariable logistic regression, p=0.026; OR=3.36; 95% CI: 1.16–9.76). This difference remained significant after accounting for prematurity (multivariable logistic regression, Padj=0.011, OR=5.15, 95% CI: 1.47–18.09). No differences were observed in the distributions of GPX1 and SOD2 genotypes (p=0.816 and p=0.588). Conclusions Common GPX1, SOD2 and CAT polymorphisms influence neither the overall risk for epilepsy nor the risk for epilepsy after HIBI. CAT rs1001179 is associated with development of cerebral palsy after HIBI.