Naslov
Gene polymorphisms linked to myelin lipid metabolism and antioxidative pathway may contribute to cerebral palsy etiopathogenesis

Autori
Kalanj Bognar, Svjetlana ; Mlinac Jerković, Kristina ; Ilić, Katarina

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Society for Neuroscience (SfN) Meeting Planner / - , 2018, 795-796

Skup
Society for Neuroscience (SfN) Meeting 2018

Mjesto i datum
San Diego (CA), Sjedinjene Američke Države, 03.11.2018. - 07.11.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
cerabral palsy ; arylsulfatase A ; glutathione S-transferase P1

Sažetak
In spite of improved maternal, obstetric and neonatal care there has been no significant change of the cerebral palsy (CP) prevalence around the world, which indicates a contribution of non- recognized genetic factors in CP pathogenesis. Complexity and heterogeneous clinical presentation of CP is related to different spatial/temporal distribution of immature brain injuries and abnormal brain development. Neuroimaging studies showed that white matter injury is the most common finding in CP. Integrity of white matter depends on many factors, including regulated metabolism of specific myelin lipids and ability of myelin to respond to oxidative damage. The rationale of this study is based on the following facts: first, demyelination may be associated with altered degradation and accumulation of sulfatides, abundant lipids of oligodendrocyte membranes ; second, prenatal or postnatal hypoxia/ischemia is considered as one of the most important factors in CP pathogenesis, and may lead to destruction of white matter ; third, glutathione detoxification pathway is common cellular antioxidative protection system ; fourth, decreased antioxidative capacity is shown in CP. We investigated a potential combined effect of selected candidate gene polymorphisms in CP. For that purpose, in 67 CP patients and 231 healthy individuals, we estimated frequencies of: (a) two most common mutations in arylsulfatase A (ASA) gene responsible for ASA pseudodeficiency (ASA- PD), a condition associated with lower ASA enzyme activity and reported in several neuropsychiatric disorders ; (b) two glutathione S-transferase P1 (GSPT1) polymorphisms shown to be involved in diseases characterized by various levels of cellular oxidative damage.We did not find significantly different frequencies of ASA-PD mutations in CP vs. controls. Interestingly, ASA enzyme activities were in lower range in more than 70% of CP patients, due to unknown genetic or epigenetic factors influencing ASA catalytic properties. In the case of C341T GSTP1 polymorphism, we found significantly higher frequency of the mutated T allele in CP vs. healthy subjects (6% vs. 27%, p<0.05, chi-square). Also, we didn't find any homozygous TT genotype in CP while in healthy subjects its frequency is 8%. Higher frequency of C341T mutation in controls may indicate its protective role, and contribute to more efficient antioxidative capacity by glutathione S-transferase pathway in healthy individuals. In conclusion, genes related to cellular antioxidative protection and myelin integrity and metabolism seem to be promissing candidates for studying genetic factors involved in complex etiopathogenesis of cerebral palsy.

Izvorni jezik
Engleski

POVEZANOST RADA