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Surfactant protein B polymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma.

ABSTRACT: Surfactant proteins (SP) are important for the innate host defence and essential for a physiological lung function. Several linkage and association studies have investigated the genes coding for different surfactant proteins in the context of pulmonary diseases such as chronic obstructive pulmonary disease or respiratory distress syndrome of preterm infants. In this study we tested whether SP-B was in association with two further pulmonary diseases in children, i. e. severe infections caused by respiratory syncytial virus and bronchial asthma.We chose to study five polymorphisms in SP-B: rs2077079 in the promoter region; rs1130866 leading to the amino acid exchange T131I; rs2040349 in intron 8; rs3024801 leading to L176F and rs3024809 resulting in R272H. Statistical analyses made use of the Armitage's trend test for single polymorphisms and FAMHAP and FASTEHPLUS for haplotype analyses.The polymorphisms rs3024801 and rs3024809 were not present in our study populations. The three other polymorphisms were common and in tight linkage disequilibrium with each other. They did not show association with bronchial asthma or severe RSV infection in the analyses of single polymorphisms. However, haplotypes analyses revealed association of SP-B with severe RSV infection (p = 0.034).Thus our results indicate a possible involvement of SP-B in the genetic predisposition to severe RSV infections in the German population. In order to determine which of the three polymorphisms constituting the haplotypes is responsible for the association, further case control studies on large populations are necessary. Furthermore, functional analysis need to be conducted.

SUBMITTER: Puthothu B

PROVIDER: S-EPMC1877814 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Surfactant protein B polymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma.

Puthothu Beena B Forster Johannes J Heinze Jessica J Heinzmann Andrea A Krueger Marcus M

BMC pulmonary medicine 20070511

<h4>Background</h4>Surfactant proteins (SP) are important for the innate host defence and essential for a physiological lung function. Several linkage and association studies have investigated the genes coding for different surfactant proteins in the context of pulmonary diseases such as chronic obstructive pulmonary disease or respiratory distress syndrome of preterm infants. In this study we tested whether SP-B was in association with two further pulmonary diseases in children, i. e. severe in ...[more]

PMID: 17498296

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Project description:Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection-related hospitalization in the first year of life. Surfactant dysfunction is central to pathophysiologic mechanisms of various pulmonary diseases including RSV. We hypothesized that RSV severity is associated with single nucleotide polymorphisms (SNPs) of surfactant proteins (SPs). We prospectively enrolled 405 RSV-positive children and divided them into moderate and severe RSV disease. DNA was extracted and genotyped for sixteen specific SP gene SNPs. SP-A1 and A2 haplotypes were assigned. The association of RSV severity with SP gene SNPs was investigated by multivariate logistic regression. A likelihood ratio test was used to test the goodness of fit between two models (one with clinical and demographic data alone and another that included genetic variants). p ≤ 0.05 denotes statistical significance. A molecular dynamics simulation was done to determine the impact of the SFTPA2 rs1965708 on the SP-A behavior under various conditions. Infants with severe disease were more likely to be younger, of lower weight, and exposed to household pets and smoking, as well as having co-infection on admission. A decreased risk of severe RSV was associated with the rs17886395_C of the SFTPA2 and rs2243639_A of the SFTPD, whereas an increased risk was associated with the rs1059047_C of the SFTPA1. RSV severity was not associated with SNPs of SFTPB and SFTPC. An increased risk of severe RSV was associated with the 1A0 genotype of SFTPA2 in its homozygous or heterozygous form with 1A3. A molecular dynamic simulation study of SP-A variants that differ in amino acid 223, an important amino acid change (Q223K) between 1A0 and 1A3, showed no major impact on the behavior of these two variants except for higher thermodynamic stability of the K223 variant. The likelihood ratio test showed that the model with multi-allelic variants along with clinical and demographic data was a better fit to predict RSV severity. In summary, RSV severity was associated with hydrophilic (but not with hydrophobic) SPs gene variants. Collectively, our findings show that SP gene variants may play a key role in RSV infection and have a potential role in prognostication.

Project description:BackgroundWe sought to identify predictors of asthma development following severe early childhood RSV bronchiolitis. Different definitions of asthma were also compared.MethodsThis longitudinal, observational study (N = 343) followed patients (<2 years old) from a placebo-controlled trial (N = 979) of montelukast after RSV bronchiolitis to identify clinical, demographic, or biochemical predictors of asthma, atopic disorders, and chronic asthma therapy use at 6 years of age (Clinical Trials Registry Number: NCT01140048). Asthma (primary definition) was based on parental identification of wheeze at 6 AND 12 months before 6 years of age; definitions based on physician diagnosis as well as parental identification of wheeze at 6 OR 12 months (to consider seasonal effect) were also assessed. Post-hoc analyses evaluated agreement among asthma diagnosis criteria.ResultsPrevalence of asthma (primary definition by parental identification), asthma (physician diagnosis), atopic disorders, and chronic asthma therapy use (parental identification) was 6.1%, 22.4%, 36.2%, and 14.5%, respectively. Predictors for asthma (primary definition) included male gender, a relative with asthma, and RAST positive for dog dander; for physician diagnosis of asthma, high severity score for RSV bronchiolitis, high respiratory rate, and asthma diagnosis before enrollment. Predictors of atopic disorders included allergic rhinitis before enrollment, a relative with asthma, and the plasma biomarkers IL-5, IL-16, and IL-18. Predictors of chronic asthma therapy use included asthma diagnosis before enrollment and geographic region (Europe and Africa). Only 42% of patients with asthma (primary definition) also met the asthma definition by physician diagnosis and chronic asthma therapy use.ConclusionAmong children with early RSV bronchiolitis, hereditary factors (i.e., having a relative with asthma) and RSV bronchiolitis severity were predictors of asthma and atopic disorders at 6 years of age. Of interest, there was poor agreement among the asthma definitions evaluated. Pediatr Pulmonol. 2016;51:1382-1392. © 2016 Wiley Periodicals, Inc.

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Surfactant protein B polymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma.

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Surfactant protein B polymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma.

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