Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiology of bronchopulmonary dysplasia (BPD) as an inflammatory disorder secondary to neonatal respiratory distress syndrome (RDS) is not yet fully understood and still represents a major complication of prematurity. The main pathophysiologic feature of RDS is a primary surfactant deficiency in a structurally immature lung. Pulmonary surfactant contains 90 percent phospholipids and 10 percent proteins (surfactant proteins A, B, C, and D). As surfactant protein A (SP-A) has several major immunological and metabolic intrapulmonary functions, we aimed at investigating an association of polymorphisms of SP-A1 and SP-A2 encoding genes and the risk of BPD. We performed a case-control study exclusively including Caucasian preterm infants below 32 weeks of gestation matched for the degree of immaturity and the year of birth. Venous cord blood was taken prospectively and analyzed by polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), cloning and sequencing. BPD was defined as oxygen dependency or need for mechanical ventilation at day 28. Twenty-three infants with BPD were enrolled (mean gestational age 26.2 weeks; mean birth weight 760.4 g) and compared with 23 infants matched on the basis of gestational age (mean gestational age 27.9 weeks; mean birthweight 1015 g). We observed a significantly increased frequency of the SP-A1 polymorphism 6A6 in infants with BPD compared with controls. In addition to previously established risk factors for BPD, 6A6 polymorphism for SP-A1 gene is an independent co-factor. We believe treatment of neonatal RDS should also include stratification according to genetic risk factors.
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PMID:Polymorphisms of surfactant protein A genes and the risk of bronchopulmonary dysplasia in preterm infants. 1110 14

Respiratory distress syndrome (RDS) is a multifactorial developmental disease caused by lung immaturity and presenting as high-permeability lung edema ("hyaline membrane disease"). It is characterized by a transient deficiency of alveolar surfactant during the first week of life. During the first few days of life, the alveolar surfactant pool size increases up to that in the controls. The allelic variants of the genes encoding the surfactant proteins (SP) SP-A1, SP-A2, SP-B, and SP-C have been associated with RDS. The main SP-A haplotype, interactively with the SP-B Ile131Thr polymorphism and with constitutional and environmental factors, influence the risk. Case reports on mutations with partially functional SP-B have been published. The genetic susceptibility factors depend on the degree of prematurity at birth, consistent with sequential differentiation of the lung and gestation-dependent differences in clinical presentation. The preferentially type 2 cell expressed genes involved in critical functions (such as ATP-binding cassette transporter, ABCA3), those involved in susceptibility to acute lung damage, and those with known susceptibility to other severe lung diseases (such as G protein-coupled receptor for asthma susceptibility, GPR154 alias GPRA) will possibly serve as candidate genes in future studies. RDS associated with near-term and term births may have a different genetic predisposition and pathogenesis compared to RDS after very preterm birth. As we learn more about the molecular consequences of allelic variation, new therapies based on a new generation of surfactant diagnostics and individualized therapies may follow.
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PMID:Genetic basis of respiratory distress syndrome. 1712 71