Surfactant proteins A and B as interactive genetic determinants of neonatal respiratory distress syndrome

Haataja, Ritva

doi:10.1093/hmg/9.18.2751

Cited by 101 publications

(92 citation statements)

References 53 publications

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“…We did not have sufficient power to pursue the contribution of these more rare mutations to the disease-based risk for RDS in our neonatal intensive care unit cohort that was not enriched for lethal RDS. Common variants in SFTPB and SFTPC with minor allele frequencies Ն0.2 have also been associated with the risk for RDS, but the mechanisms by which these variants and combinations thereof impart risk are undetermined (27)(28)(29)(30). To our knowledge, the contribution of common variants in ABCA3 to the risk of RDS has not been evaluated.…”

Section: Discussionmentioning

confidence: 99%

Population and Disease-Based Prevalence of the Common Mutations Associated With Surfactant Deficiency

et al. 2008

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ABSTRACT:The prevalence of the common mutations in the surfactant protein-B (121ins2), surfactant protein-C (I73T), and ATP-binding cassette member A3 (E292V) genes in populationbased or case-control cohorts of newborn respiratory distress syndrome (RDS) is unknown. We determined the frequencies of these mutations in ethnically diverse population and disease-based cohorts using restriction enzyme analysis (121ins2 and E292V) and a 5Ј nuclease assay (I73T) in DNA samples from population-based cohorts in Missouri, Norway, South Korea, and South Africa, and from a case-control cohort of newborns with and without RDS (n ϭ 420). We resequenced the ATP-binding cassette member A3 gene (ABCA3) in E292V carriers and computationally inferred ABCA3 haplotypes. The population-based frequencies of 121ins2, E292V, and I73T were rare (Ͻ0.4%). E292V was present in 3.8% of newborns with RDS, a 10-fold greater prevalence than in the Missouri cohort (p Ͻ 0.001). We did not identify other loss of function mutations in ABCA3 among patients with E292V that would account for their RDS. E292V occurred on a unique haplotype that was derived from a recombination of two common ABCA3 haplotypes. E292V was over-represented in newborns with RDS suggesting that E292V or its unique haplotype impart increased genetic risk for RDS. (Pediatr Res 63: 645-649, 2008)

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Section: Discussionmentioning

confidence: 99%

Population and Disease-Based Prevalence of the Common Mutations Associated With Surfactant Deficiency

et al. 2008

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“…Certain SP-A alleles and an SNP in the SP-B gene have been shown to associate interactively with RDS in premature infants. 9 The SP-C gene is short, spanning only 3500 base pairs on the short arm of chromosome 8 (8p23.1) near the gene coding for bone morphogenetic protein-1 (BMP-1). 10 -13 The extent of allelic variation and the distribution of different SP-C alleles in the general population have not been examined in detail.…”

Section: Introductionmentioning

confidence: 99%

Surfactant protein C gene variation in the Finnish population – association with perinatal respiratory disease

2004

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Surfactant protein C (SP-C) is a small hydrophobic protein component of alveolar surfactant, a lipidprotein complex lining the alveolar surface of the lung. Surfactant deficiency is the main cause of respiratory distress syndrome (RDS) in premature infants. RDS is a major risk factor of a chronic lung disease called bronchopulmonary dysplasia (BPD). The dominant mutations of the SP-C gene have recently been associated with interstitial lung diseases. However, the common genetic variation in the surfactant protein C gene has not been studied in detail. In the present study, the exonic variation of the SP-C gene in the Finnish population (n ¼ 472) was defined, and the association of the allelic variants with the susceptibility to RDS and BPD was examined. Conformation-sensitive gel electrophoresis (CSGE) was used to determine the extent of exonic variation in the SP-C gene. Methods of genotyping were generated for three biallelic polymorphisms of the SP-C gene's exons 1, 4 and 5, which encode proSP-C. The frequencies of these polymorphisms were evaluated in a study population consisting of 158 DNA samples from fullterm infants. In addition, the linkage disequilibrium between the SP-C alleles was evaluated by haplotype analysis of parent -infant triplets. The role of SP-C gene variation in RDS and in BPD was evaluated in a high-risk population of 245 premature infants. According to the present results, the SP-C polymorphisms were associated with RDS and with very premature birth. The strength of allelic associations differed according to the gender of the premature infants.

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“…This applies to other surfactant protein genes as well, and they have recently been studied as candidates for multifactorial diseases. Associations of certain surfactant protein A (SP-A) and surfactant protein B (SP-B) alleles with the risk of neonatal respiratory distress syndrome have been established (7)(8)(9). An association of a SP-D allele with a risk for tuberculosis in a Mexican population was reported recently (10).…”

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Surfactant Protein D Gene Polymorphism Associated with Severe Respiratory Syncytial Virus Infection

et al. 2002

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Respiratory syncytial virus (RSV) is the major respiratory tract pathogen in infancy. Host-related differences in susceptibility to severe RSV infection suggest that genetic factors may play a role. In this study, a candidate-gene approach was used to study whether the surfactant protein D (SP-D) gene polymorphism associates with severe RSV infection. DNA samples from 84 infants hospitalized for the treatment of RSV bronchiolitis and 93 healthy controls were analyzed. The controls were matched with the cases on the basis of sex, hospital district, date of birth (Ϯ2 wk) and gestational age at birth (Ϯ2 wk). Three biallelic SP-D gene polymorphisms were genotyped. Significant differences were observed in the SP-D allele frequencies for amino acid 11 between the RSV infants and their matched controls. The frequency of the allele coding for Met 11 (p ϭ 0.033) was increased in the severe RSV group. The frequency of the homozygous genotype Met/Met for amino acid 11 was increased in the RSV group relative to the controls, whereas the heterozygous genotype tended to be less frequent among the RSV cases than in the matched controls. Conditional logistic regression analysis was used to study whether the confounders, i.e. smoking and number of children in the family, influence the association between the homozygous SP-D genotype for methionine 11 and the risk of RSV bronchiolitis. The results further confirmed this association (p ϭ 0.028). To our knowledge, the present report provides the first evidence of a specific gene associated with susceptibility to severe RSV infection. Respiratory syncytial virus (RSV) is a major respiratory tract pathogen in early childhood. In young infants, seasonal epidemics of RSV cause 50% of the severe instances of bronchiolitis that require hospital treatment and may be fatal. Environmental factors, gender, and socioeconomic status all play a role in RSV infections, but the host-related differences in susceptibility suggest that genetic factors contribute to the risk of contracting this disease (1).Pulmonary surfactant, a complex mixture of phospholipids and surfactant proteins, lines the alveolar surface of the lung and is essential for normal respiratory function. Surfactant protein D (SP-D) was first described in association with alveolar surfactant. However, this protein does not bind to the surfactant complex and has been found elsewhere in the airways. SP-D is a collagenous C-type lectin mainly assembled as dodecamers consisting of four homotrimeric subunits. SP-D has several immunomodulatory functions, including agglutination of some viruses that cause airway disease (2).Concentrations of the surfactant components are decreased in viral bronchiolitis (3, 4). Studies with a mouse model have shown dysfunction of the surfactant complex in RSV induced pulmonary infections (5). Hickling et al. (6) showed that intranasal administration of recombinant SP-D domain to RSV-infected mice reduced the levels of lung virus by 80%, suggesting that SP-D plays a major role in clearing RSV from the lu...

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Surfactant proteins A and B as interactive genetic determinants of neonatal respiratory distress syndrome

Cited by 101 publications

References 53 publications

Population and Disease-Based Prevalence of the Common Mutations Associated With Surfactant Deficiency

Population and Disease-Based Prevalence of the Common Mutations Associated With Surfactant Deficiency

Surfactant protein C gene variation in the Finnish population – association with perinatal respiratory disease

Surfactant Protein D Gene Polymorphism Associated with Severe Respiratory Syncytial Virus Infection

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