Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476273 (respiratory distress)
 19,632 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deficiency of the lipoprotein complex, surfactant, can lead to respiratory distress syndrome (RDS) in the prematurely born infant. The surfactant proteins (SP) play important roles in the function of surfactant. Previously, we have characterized four allelic variants of the SP-A1 gene (6A, 6A2, 6A3, and 6A4) and five allelic variants of the SP-A2 gene (1A, 1A0, 1A1, 1A2, and 1A3). We hypothesized that specific SP-A alleles/genotypes are associated with increased risk of RDS. Because race, gestational age (GA), and sex are risk factors for RDS, we first studied the distribution and frequencies of SP-A alleles/genotypes while adjusting for these factors as confounders or effect modifiers in control (n = 86 white and 12 black subjects) and RDS (n = 106 white and 37 black subjects) populations with GAs ranging from 24 wk to term. Although the odds ratios of several alleles and genotypes were in the opposite directions for black and white subjects, the homogeneity of odds ratio reached statistical significance only in the case of 6A3/6A3. Although differences were observed in subgroups with different GAs (< or =28 and >28 wk) of the RDS white population, definitive conclusions cannot be made regarding the effect of modification by GA. No differences were observed as a function of sex. Second, we compared the frequencies of SP-A genotypes and alleles between control (n = 83) and RDS (n = 82) patients in the >28-wk white population. Differences between the two groups were observed for the 1A0 allele and 1A0 genotypes. Moreover, a significant synergistic positive association was observed between 1A0 allele + SP-B polymorphic variant and RDS. We conclude that 1) the genetic analyses of RDS and SP-A locus should be performed separately for black and white populations and 2) SP-A alleles/genotypes and SP-B variant may contribute to the etiology of RDS and/or may serve as markers for disease subgroups.
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PMID:Association of pulmonary surfactant protein A (SP-A) gene and respiratory distress syndrome: interaction with SP-B. 947 80

The use of candidate genes has increased the ability to identify genetic factors involved in diseases with complex and multifactorial etiology. The surfactant proteins (SP) A and D are involved in host defense and inflammatory processes of the lung, which are often components of pulmonary disease. Therefore, the SP-A and SP-D genes make particularly good candidates to study factors contributing to pulmonary disease etiopathogenesis. Moreover, SP-A also plays a role in the surface tension lowering abilities of pulmonary surfactant, which is essential for normal lung function. Although genetic variability at the SP-D locus may exist among humans, allelic variants have not yet been characterized. On the other hand, the human SP-A genes (SP-A1 and SP-A2) are characterized by genetically dependent splice variants at the 5' untranslated region and allelic variants. The polymorphisms that give rise to SP-A1 and SP-A2 alleles are contained within coding regions, potentially having an effect on protein function. There appears to be a correlation between SP-A genotype and SP-A mRNA content. Furthermore, one SP-A2 allele (1A0) shown to associate with low SP-A mRNA levels is found with higher frequency in a subgroup with respiratory distress syndrome. The evidence gathered thus far indicates that SP-A, possibly by interacting with other surfactant components, may play a role (e.g. be a susceptibility factor) in the development of respiratory disease.
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PMID:Genetics of the hydrophilic surfactant proteins A and D. 981 81

An allele association study of 19 polymorphisms in surfactant proteins SP-A1, SP-A2, SP-B, and SP-D genes in acute respiratory distress syndrome (ARDS) was carried out. Trend-test analysis revealed differences (p < 0.05) in the frequency of alleles for some of the microsatellite markers flanking SP-B, and for one polymorphism (C/T) at nucleotide 1580 [C/T (1580)], within codon 131 (Thr131Ile) of the SP-B gene. The latter determines the presence or absence of a potential N-linked glycosylation site. Multivariate analysis revealed significant differences only for the C/T (1580) polymorphism. When the ARDS population was divided into subgroups, idiopathic (i.e., pneumonia, etc.) or exogenic (i.e., trauma, etc.), significant differences were observed for the C/T (1580), for the idiopathic ARDS group, and the frequency of the C/C genotype was increased in this group. Based on the odds ratio, the C allele may be viewed as a susceptibility factor for ARDS. Although the expression of both C and T alleles occurs in heterozygous individuals, it is currently not known whether these alleles correspond to similar levels of SP-B protein. These data suggest that SP-B or a linked gene contributes to susceptibility to ARDS.
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PMID:Polymorphisms of human SP-A, SP-B, and SP-D genes: association of SP-B Thr131Ile with ARDS. 1107 40

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

Interactive genetic and environmental factors may influence the differentiation of surfactant and the risk of respiratory distress syndrome (RDS). DNA samples from 441 premature singleton infants and 480 twin or multiple infants were genotyped for surfactant-specific protein (SP)-A1, SP-A2, and SP-B exon 4 polymorphisms and intron 4 size variants in a homogeneous white population. Distributions of the SP-A and SP-B gene variants between RDS and no-RDS infants were determined alone and in combination. SP-A1 allele 6A2 (p = 0.009) and the homozygous genotype 6A2/6A2 (p = 0.003) were overrepresented in RDS of singletons when the SP-B exon 4 genotype was Thr/Thr, and underrepresented in RDS of multiples when the SP-B genotype was Ile/Thr (p = 0.012 for 6A2 and p = 0.03 for 6A2/6A2) or Thr/Thr (p = 0.12 for 6A2 and p = 0.018 for 6A2/6A2, respectively). The SP-A 6A2 allele in the SP-B Thr131 background predisposed the smallest singleton infants to RDS, whereas near-term multiples were protected from RDS. There was a continuous association between fetal mass and risk of RDS, defined by the SP-A and SP-B variants. Labeled lung explants with the Thr/Thr genotype showed proSP-B amino-terminal glycosylation, which was absent in Ile/Ile samples. Genetic and environmental variation may influence intracellular processing of surfactant complex and the susceptibility to RDS.
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PMID:Surfactant protein A and B genetic variants in respiratory distress syndrome in singletons and twins. 1294 25

Here, we describe the approach of defining the genetic contribution to disease and discuss the polymorphisms of some genes that are associated with respiratory disease. The common allelic variants of SP-A1, SP-A2, SP-B, SP-C, and SP-D genes are associated with respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), or respiratory syncytial virus (RSV) bronchiolitis. The main SP-A haplotype, interactively with SP-B Ile131Thr polymorphism and with constitutional and environmental factors, influences the risk of RDS. The polymorphisms of SP-A2 and SP-D are associated with the risk of severe RSV. The polymorphism may turn out to be important in susceptibility to influenza virus. The SP-B intron 4 deletion variant is the risk factor of BPD. Understanding the molecular mechanisms behind the hereditary risk may lead to new focused treatment strategies.
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PMID:Surfactant protein polymorphisms and neonatal lung disease. 1714 61

Surfactant associated protein-A (SP-A) is the most abundant pulmonary surfactant protein and belongs to the family of innate host defense proteins termed collectins. Besides pulmonary host defense, SP-A is also involved in the formation of pulmonary surfactant, as it is essential for the structure of tubular myelin. The human SP-A gene locus includes two functional genes, SFTPA1 and SFTPA2 which are expressed independently, and a pseudo gene. The largest amount of SP-A1 proteins assemble to larger molecular complexes, whereas SP-A2 forms mainly dimers and trimers. SP-A polymorphisms play a role in respiratory distress syndrome, allergic bronchopulmonary aspergillosis and idiopathic pulmonary fibrosis. The levels of SP-A are decreased in the lungs of patients with cystic fibrosis, respiratory distress syndrome and further chronic lung diseases. Future areas for clinical research include disease specific SP-A expression pattern and their functional consequences, the differential roles of SP-A1 and SP-A2 in human lung diseases, and therapeutical approaches to correct altered SP-A levels.
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PMID:Surfactant protein A--from genes to human lung diseases. 1716 48