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Published in: BMC Pulmonary Medicine 1/2007

Open Access 01-12-2007 | Research article

Surfactant protein Bpolymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma

Authors: Beena Puthothu, Johannes Forster, Jessica Heinze, Andrea Heinzmann, Marcus Krueger

Published in: BMC Pulmonary Medicine | Issue 1/2007

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

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.
Literature
1.
go back to reference Johansson J, Curstedt T: Molecular structures and interactions of pulmonary surfactant components. Eur J Biochem. 1997, 244: 675-93. 10.1111/j.1432-1033.1997.00675.x.CrossRefPubMed Johansson J, Curstedt T: Molecular structures and interactions of pulmonary surfactant components. Eur J Biochem. 1997, 244: 675-93. 10.1111/j.1432-1033.1997.00675.x.CrossRefPubMed
2.
go back to reference Phelps DS: Surfactant regulation of host defense function in the lung: a question of balance. Pediatr Pathol Mol Med. 2001, 0: 269-92. 10.1080/152279501750412225.CrossRef Phelps DS: Surfactant regulation of host defense function in the lung: a question of balance. Pediatr Pathol Mol Med. 2001, 0: 269-92. 10.1080/152279501750412225.CrossRef
3.
go back to reference Nogee LM, Garnier G, Dietz HC, Singer L, Murphy AM, deMello DE, Colten HR: A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds. J Clin Invest. 1994, 93: 1860-3.CrossRefPubMedPubMedCentral Nogee LM, Garnier G, Dietz HC, Singer L, Murphy AM, deMello DE, Colten HR: A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds. J Clin Invest. 1994, 93: 1860-3.CrossRefPubMedPubMedCentral
4.
go back to reference Lewis JF, Jobe AH: Surfactant and the adult respiratory distress syndrome. Am Rev Respir Dis. 1993, 147: 218-33.CrossRefPubMed Lewis JF, Jobe AH: Surfactant and the adult respiratory distress syndrome. Am Rev Respir Dis. 1993, 147: 218-33.CrossRefPubMed
5.
go back to reference Lin Z, deMello DE, Wallot M, Floros J: An SP-B gene mutation responsible for SP-B deficiency in fatal congenital alveolar proteinosis: evidence for a mutation hotspot in exon 4. Mol Genet Metab. 1998, 64: 25-35. 10.1006/mgme.1998.2702.CrossRefPubMed Lin Z, deMello DE, Wallot M, Floros J: An SP-B gene mutation responsible for SP-B deficiency in fatal congenital alveolar proteinosis: evidence for a mutation hotspot in exon 4. Mol Genet Metab. 1998, 64: 25-35. 10.1006/mgme.1998.2702.CrossRefPubMed
6.
go back to reference Vamvakopoulos NC, Modi WS, Floros J: Mapping the human pulmonary surfactant-associated protein B gene (SFTP3) to chromosome 2p12--> p11.2. Cytogenet Cell Genet. 1995, 68: 8-10.CrossRefPubMed Vamvakopoulos NC, Modi WS, Floros J: Mapping the human pulmonary surfactant-associated protein B gene (SFTP3) to chromosome 2p12--> p11.2. Cytogenet Cell Genet. 1995, 68: 8-10.CrossRefPubMed
7.
go back to reference Hawgood S, Derrick M, Poulain F: Structure and properties of surfactant protein B. Biochim Biophys Acta. 1998, 1408: 150-60.CrossRefPubMed Hawgood S, Derrick M, Poulain F: Structure and properties of surfactant protein B. Biochim Biophys Acta. 1998, 1408: 150-60.CrossRefPubMed
8.
go back to reference Sigurs N, Gustafsson PM, Bjarnason R, Lundberg F, Schmidt S, Sigurbergsson F, Kjellman B: Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. J Respir Crit Care Med. 2005, 171: 137-41. 10.1164/rccm.200406-730OC.CrossRef Sigurs N, Gustafsson PM, Bjarnason R, Lundberg F, Schmidt S, Sigurbergsson F, Kjellman B: Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. J Respir Crit Care Med. 2005, 171: 137-41. 10.1164/rccm.200406-730OC.CrossRef
9.
go back to reference Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B: Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med. 2000, 161: 1501-7.CrossRefPubMed Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B: Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med. 2000, 161: 1501-7.CrossRefPubMed
10.
go back to reference Stein RT, Sherrill D, Morgan W, Holberg CJ, Halonen M, Taussig LM, Wright AL, Martinez FD: Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet. 1999, 354: 541-5. 10.1016/S0140-6736(98)10321-5.CrossRefPubMed Stein RT, Sherrill D, Morgan W, Holberg CJ, Halonen M, Taussig LM, Wright AL, Martinez FD: Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet. 1999, 354: 541-5. 10.1016/S0140-6736(98)10321-5.CrossRefPubMed
11.
go back to reference Forster J, Ihorst G, Rieger CH, Stephan V, Frank HD, Gurth H, et al: Prospective population-based study of viral lower respiratory tract infections in children under 3 years of age (the PRI.DE study). Eur J Pediatr. 2004, 163: 709-16. 10.1007/s00431-004-1523-9.CrossRefPubMed Forster J, Ihorst G, Rieger CH, Stephan V, Frank HD, Gurth H, et al: Prospective population-based study of viral lower respiratory tract infections in children under 3 years of age (the PRI.DE study). Eur J Pediatr. 2004, 163: 709-16. 10.1007/s00431-004-1523-9.CrossRefPubMed
12.
go back to reference Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Lancet. 1998, 351: 1225-32. 10.1016/S0140-6736(97)07302-9. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Lancet. 1998, 351: 1225-32. 10.1016/S0140-6736(97)07302-9.
13.
go back to reference Heinzmann A, Jerkic SP, Ganter K, Kurz T, Blattmann S, Schuchmann L, Gerhold K, et al: Association study of the variant Arg110Gln in Interleukin-13 with atopic diseases and juvenile idiopathic arthritis. J All Clin Immunol. 2003, 112: 743-47. 10.1016/S0091-6749(03)01887-6.CrossRef Heinzmann A, Jerkic SP, Ganter K, Kurz T, Blattmann S, Schuchmann L, Gerhold K, et al: Association study of the variant Arg110Gln in Interleukin-13 with atopic diseases and juvenile idiopathic arthritis. J All Clin Immunol. 2003, 112: 743-47. 10.1016/S0091-6749(03)01887-6.CrossRef
14.
go back to reference Sanger F, Nicklen S, Coulson AR: DNA sequencing with chain-terminating inhibitors. Biotechnology. 1992, 24: 104-8.PubMed Sanger F, Nicklen S, Coulson AR: DNA sequencing with chain-terminating inhibitors. Biotechnology. 1992, 24: 104-8.PubMed
15.
go back to reference Sasieni PD: From genotypes to genes: doubling the sample size. Biometrics. 1997, 53: 1253-61. 10.2307/2533494.CrossRefPubMed Sasieni PD: From genotypes to genes: doubling the sample size. Biometrics. 1997, 53: 1253-61. 10.2307/2533494.CrossRefPubMed
16.
go back to reference Zhao JH, Sham PC: Faster haplotype frequency estimation using unrelated subjects. Hum Hered. 2002, 53: 36-41. 10.1159/000048602.CrossRefPubMed Zhao JH, Sham PC: Faster haplotype frequency estimation using unrelated subjects. Hum Hered. 2002, 53: 36-41. 10.1159/000048602.CrossRefPubMed
17.
go back to reference Becker T, Knapp M: Maximum-likelihood estimation of haplotype frequencies in nuclear families. Genet Epidemiol. 2004, 27: 21-32. 10.1002/gepi.10323.CrossRefPubMed Becker T, Knapp M: Maximum-likelihood estimation of haplotype frequencies in nuclear families. Genet Epidemiol. 2004, 27: 21-32. 10.1002/gepi.10323.CrossRefPubMed
18.
go back to reference Revak SD, Merritt TA, Degryse E, Stefani L, Courtney M, Hallman M, Cochrane CG: Use of human surfactant low molecular weight apoproteins in the reconstitution of surfactant biologic activity. J Clin Invest. 1988, 8: 826-33.CrossRef Revak SD, Merritt TA, Degryse E, Stefani L, Courtney M, Hallman M, Cochrane CG: Use of human surfactant low molecular weight apoproteins in the reconstitution of surfactant biologic activity. J Clin Invest. 1988, 8: 826-33.CrossRef
19.
go back to reference Erpenbeck VJ, Schmidt R, Gunther A, Krug N, Hohlfeld JM: Surfactant protein levels in bronchoalveolar lavage after segmental allergen challenge in patients with asthma. Allergy. 2006, 61: 598-604. 10.1111/j.1398-9995.2006.01062.x.CrossRefPubMed Erpenbeck VJ, Schmidt R, Gunther A, Krug N, Hohlfeld JM: Surfactant protein levels in bronchoalveolar lavage after segmental allergen challenge in patients with asthma. Allergy. 2006, 61: 598-604. 10.1111/j.1398-9995.2006.01062.x.CrossRefPubMed
20.
go back to reference Puthothu B, Krueger M, Heinze J, Forster J, Heinzmann A: Haplotpyes of Surfactant Protein C are associated with common paediatric lung diseases. Pediatr Allergy Immunol. 2006, 17: 572-577. 10.1111/j.1399-3038.2006.00467.x.CrossRefPubMed Puthothu B, Krueger M, Heinze J, Forster J, Heinzmann A: Haplotpyes of Surfactant Protein C are associated with common paediatric lung diseases. Pediatr Allergy Immunol. 2006, 17: 572-577. 10.1111/j.1399-3038.2006.00467.x.CrossRefPubMed
21.
go back to reference Floros J, Fan R, Diangelo S, Guo X, Wert J, Luo J: Surfactant protein (SP) B associations and interactions with SP-A in white and black subjects with respiratory distress syndrome. Pediatr Int. 2001, 43: 567-76. 10.1046/j.1442-200X.2001.01474.x.CrossRefPubMedPubMedCentral Floros J, Fan R, Diangelo S, Guo X, Wert J, Luo J: Surfactant protein (SP) B associations and interactions with SP-A in white and black subjects with respiratory distress syndrome. Pediatr Int. 2001, 43: 567-76. 10.1046/j.1442-200X.2001.01474.x.CrossRefPubMedPubMedCentral
22.
go back to reference Seifart C, Plagens A, Brodje D, Muller B, von Wichert P, Floros J: Surfactant protein B intron 4 variation in German patients with COPD and acute respiratory failure. Dis Markers. 2002, 18: 129-36.CrossRefPubMedPubMedCentral Seifart C, Plagens A, Brodje D, Muller B, von Wichert P, Floros J: Surfactant protein B intron 4 variation in German patients with COPD and acute respiratory failure. Dis Markers. 2002, 18: 129-36.CrossRefPubMedPubMedCentral
23.
go back to reference Jacobs KA, Phelps DS, Steinbrink R, Fisch J, Kriz R, Mitsock L, Dougherty JP, Taeusch HW, Floros J: Isolation of a cDNA clone encoding a high molecular weight precursor to a 6-kDa pulmonary surfactant-associated protein. J Biol Chem. 1987, 262: 9808-11.PubMed Jacobs KA, Phelps DS, Steinbrink R, Fisch J, Kriz R, Mitsock L, Dougherty JP, Taeusch HW, Floros J: Isolation of a cDNA clone encoding a high molecular weight precursor to a 6-kDa pulmonary surfactant-associated protein. J Biol Chem. 1987, 262: 9808-11.PubMed
Metadata
Title
Surfactant protein Bpolymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma
Authors
Beena Puthothu
Johannes Forster
Jessica Heinze
Andrea Heinzmann
Marcus Krueger
Publication date
01-12-2007
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2007
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/1471-2466-7-6

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