The Association Between LPCAT1 Genetic Polymorphism and Stress Biomarkers in Neonatal Respiratory Distress Syndrome

Neonatal respiratory distress syndrome (RDS) is caused by lung immaturity and deficiency of lung surfactant and dysfunction in preterm newborns . Surfactant is produced by type II pneumocyte that forms a bilayer of lipid over the inner surface of the alveoli. Surfactant deficiency and dysfunction lead to increased alveolar surface tension, which results in alveolar collapse and decreased lung aeration . Respiratory distress syndrome is one of the main causes of neonatal mortality . The risk of RDS increases with decreasing gestational age (GA). The incidence of RDS was estimated to be 90% in preterm neonates (GA 28 weeks or below) and to be 9% in full term neonates born at ≥38 weeks' gestation. Early diagnosis is very essential to optimize the treatment of infants with RDS.

Pathogenesis The primary cause of RDS is deficiency and/or dysfunction of surfactant which is a lipoprotein complex and is vital for normal lung function. Surfactant is synthesized, stored, and secreted by the alveolar type II cells and is primarily composed of phospholipids, which constitute 80-85% of the total mass. The remaining components of surfactant includes neutral lipids (5%-10%) and proteins (10%) . Phosphatidylcholine (PC), the most abundant phospholipid species in surfactant, constitutes 80% of the total phospholipids. There are three key enzymes involved in the PC synthesis: Lysophospholipid acyltransferase (LPCAT1, Gene ID 79888), Cholinephosphotransferase (CHPT1, Gene ID 56994) and Cholinephosphate cytidylyltransferase (PCYT1B, CPCT, Gene ID 9468). LPCAT1 is the most important enzyme in biogenesis and a key enzyme in surfactant production . LPCAT1 composed of 18 exons and is located on chromosome 5p15.33. The study of the genetic polymorphisms of surfactant-lipids related gene provides significant data about individual variability in the susceptibility to development of respiratory distress syndrome.

Neonatal stress biomarkers such as cardiac troponin (CTn) T, CTnI, NT-Terminal-pro-Brain Natriuretic Peptide (NT-pro-BNP), copeptin, and high sensitivity C-reactive protein (hs-CRP)have been considered as an indicator of perinatal asphyxia. Troponin is an inhibitory protein complex located on the actin filament in all striated muscle and consists of three subunits: T, C, and I. The asphyxiated neonate has elevated levels of cardiac troponin I (cTnI). cTnI is thought to be also an indicator of perinatal asphyxia . Neonates born after complicated delivery had significantly higher values of CTnT, CTnI and Copeptin than those born after uncomplicated delivery. The gender influence on copeptin releases . The gestational age, birth weight and duration of active labor, and membrane rupture have significant effect on hs-CRP levels.