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...
* The controls were matched to the cases for sex, hospital district, date of birth (Ϯ2 weeks) and gestational age at birth (Ϯ2 weeks). More than one control was allowed for each RSV patient. † At least one parent smokes.
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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