title: COX-1 and COX-2 polymorphisms in susceptibility to cerebral palsy in very preterm infants.
abstract: Cerebral palsy (CP) is a nonprogressive motor disorder caused by white matter damage in the developing brain. Recent epidemiological and clinical data suggest intrauterine infection/inflammation as the most common cause of preterm delivery and neonatal complications, including CP. Cyclooxygenases are key enzymes in the conversion of arachidonic acid to prostaglandins. The COX family consists of two isoforms, COX-1 and COX-2. In the brain, COX-2 is constitutively expressed at high levels on pyramidal neurons, while COX-1 is predominantly expressed by microglia and can be upregulated in pathological conditions, such as infection, ischemia and traumatic brain injury. Single nucleotide polymorphisms in the COX-1 and COX-2 gene could have profound effects on COX-1 and COX-2 expression and, directly or indirectly, influence the pathogenesis, development and severity of CP. In this study we investigated the association between single nucleotide polymorphisms of the COX-1 and COX-2 gene and susceptibility to cerebral palsy in very preterm infants. The results of our study showed the association between COX-1 high expression genotype (-842 AA) and COX-1 high expression allele -842A and risk of CP in infants with cystic periventricular leucomalacia (cPVL). Our results support an important role of COX-1 enzyme on microglial activation during neuroinflammation resulting in huge neuroinflammatory response and the proinflammatory mediator overproduction, with the serious white matter damage and CP development as a consequence.
authors.affiliation: Special Hospital for Children with Neurodevelopmental and Motor Difficulties, Goljak 2, Zagreb, Croatia. hkvidak@irb.hr.
authors.forename: Helena
authors.initials: H
authors.lastname: Kapitanović Vidak
authors.affiliation: Laboratory for Personalized Medicine, Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička c. 54, Zagreb, Croatia.
authors.forename: Tina
authors.initials: T
authors.lastname: Catela Ivković
authors.affiliation: Department of Obstetrics and Gynecology, Division of Neonatology, Clinical Hospital Merkur, Ivana Zajca 19, Zagreb, Croatia.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Vidak
authors.affiliation: Laboratory for Personalized Medicine, Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička c. 54, Zagreb, Croatia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Kapitanović
mesh_terms: D002547:Cerebral Palsy / Q000175:diagnosis / Q000235:genetics*; D002675:Child, Preschool; D051545:Cyclooxygenase 1 / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D007969:Leukomalacia, Periventricular / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human
keywords: COX-1; COX-2; Cerebral palsy; Gene polymorphisms; Very premature infants