Klinik Araştırma
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Surfaktan Protein B ve D Gen Polimorfizmlerinin Akut Bronşiolitin Sıklık ve Şiddeti Üzerine Etkileri

Yıl 2025, Cilt: 15 Sayı: 1, 1 - 5
https://doi.org/10.16899/jcm.1605226

Öz

Giriş ve Amaç: Akut bronşiolit (AB), infantlarda en yaygın hastaneye yatış nedenidir. Benzer demografik özelliklere sahip hastalar arasında bronşiolitin farklı şekilde seyretmesi, bireysel farklılıklarda genetik faktörlerin rol oynayabileceğini düşündürmektedir.
Yöntem ve Gereç: Çalışmaya bir çocuk polikliniğinden alınan, AB tanısı almış 106 bebek ve sağlıklı 107 bebek dahil edilmiştir. SP-B genindeki intron 4 ve C/A–18, ayrıca SP-D genindeki SP-D/160 (Ala160Thr) ve SP-D/270 (Ser270Thr) polimorfizmleri için genotipleme yapılmıştır.
Bulgular: SP-B intron 4 sabit polimorfizmleri olan ins/ins ve ins/del oranları, AB grubunda sırasıyla %93,40 ve %4,72, kontrol grubunda ise %84,11 ve %15,89 olarak bulunmuştur (p = 0,012). SP-D/270 (Ser270Thr) genindeki Ser/Ser ve Ser/Thr polimorfizmleri AB grubunda %60 ve %39,05, kontrol grubunda ise %79,44 ve %18,69 oranında tespit edilmiştir (p = 0,004). Ser ve Thr allel frekansları AB grubunda sırasıyla %79,90 ve %20,10, kontrol grubunda ise %88,79 ve %11,21 olarak belirlenmiştir (p = 0,012). SP-B intron 4, C/A–18 ile SP-D Ser270Thr ve Ala160Thr polimorfizmleri ile AB’nin şiddeti arasında herhangi bir ilişki bulunmamıştır (p > 0,05).
Sonuç: SP-B gen polimorfizmleri, AB için bir risk faktörü olarak belirlenirken, SP-D polimorfizmleri koruyucu bir rol oynamaktadır. Bununla birlikte, bu polimorfizmler AB’nin şiddeti ile ilişkili bulunmamıştır. Risk altındaki çocukların önceden tespit edilmesi ve yakından izlenmesi AB morbiditesi açısından önemli olabilir.

Proje Numarası

2014/53

Kaynakça

  • 1. Bria M, Coates LEC. Wheezing in Infants: Bronchiolitis, in Nelson Textbook of Pediatrics, Kliegman RM, Editor. Elsevier: Canada. 2016;2044-50.
  • 2. Gul A, Takçı Ş, Altıntaş Seyyah B, Yılmaz R. Independent Predictorsof Severity and Hospitalization in Acute Bronchiolitis: Neutrophil/Lymphocyte Ratio and Mean Platelet Volume. J Pediatr Infect Dis2018;13(04):268-73.
  • 3. Yusen RD, Cohen AH, Hamvas A. Normal lung function in subjects heterozygous for surfactant protein-B deficiency. Am J Respir Crit Care Med. 1999;159(2):411-4.
  • 4. Tokieda K, Iwamoto HS, Bachurski C, et al. Surfactant protein-B-deficient mice are susceptible to hyperoxic lung injury. Am J Respir Cell Mol Biol. 1999;21(4):463-72.
  • 5. Tokieda K, Whitsett JA, Clark JC, et al. Pulmonary dysfunction in neonatal SP-B-deficient mice. Am J Physiol. 1997;273(4):875-82.
  • 6. Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol. 2005;5(1):58-68.
  • 7. Hamvas A. Inherited surfactant protein-B deficiency and surfactant protein-C associated disease: clinical features and evaluation. Semin Perinatol. 2006;30(6):316-26.
  • 8. Kültürsay N, Uygur Ö, Yalaz M. Yenidoğan döneminde sürfaktan kullanımı-bilinenler, halen araştırılanlar, araştırılması gerekenler. Türk Ped Arş 2014;49:1-12.
  • 9. Weaver TE, Whitsett JA. Function and regulation of expression of pulmonary surfactant-associated proteins. Biochem J. 1991;273(Pt 2)(Pt 2):249-64.
  • 10. Mallory GB Jr. Surfactant proteins: role in lung physiology and disease in early life. Paediatr Respir Rev. 2001;2(2):151-8.
  • 11. Cole FS, Hamvas A, Nogee LM. Genetic disorders of neonatal respiratory function. Pediatr Res. 2001;50(2):157-62.
  • 12. Ventre K, Haroon M, Davison C. Surfactant therapy for bronchiolitis in critically ill infants. Cochrane Database Syst Rev. 2006;(3):CD005150.
  • 13. Davison C, Ventre KM, Luchetti M, Randolph AG. Efficacy of interventions for bronchiolitis in critically ill infants: a systematic review and metaanalysis. Pediatr Crit Care Med. 2004;5(5):482-9.
  • 14. Hallman M, Haataja R. Surfactant protein polymorphisms and neonatal lung disease. Semin Perinatol. 2006;30(6):350-61.
  • 15. Sorensen GL. Surfactant Protein D in Respiratory and Non-Respiratory Diseases. Front Med (Lausanne). 2018;5:18.
  • 16. Hartshorn KL, Crouch E, White MR, et al. Pulmonary surfactant proteins A and D enhance neutrophil uptake of bacteria. Am J Physiol. 1998;274(6):958-69.
  • 17. LeVine AM, Elliott J, Whitsett JA, et al. Surfactant protein-d enhances phagocytosis and pulmonary clearance of respiratory syncytial virus. Am J Respir Cell Mol Biol. 2004;31(2):193-9.
  • 18. Pavlovic J, Papagaroufalis C, Xanthou M, et al. Genetic variants of surfactant proteins A, B, C, and D in bronchopulmonary dysplasia. Dis Markers. 2006;22(5-6):277-91.
  • 19. Leth-Larsen R, Garred P, Jensenius H, et al. A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D. J Immunol. 2005;174(3):1532-8.
  • 20. Lahti M, Lofgren J, Marttila R, et al. Surfactant protein D gene polymorphism associated with severe respiratory syncytial virus infection. Pediatr Res. 2002;51(6):696-9.
  • 21. Seyyah BA. The investigation of surfactant protein B and D gene polymorphism in infants with acute bronchiolitis, in Department of Pediatrics. Gaziosmanpasa University, Tokat Turkiye. 2016;72.
  • 22. Okutan Ö, Çeltik C. Akut Bronşiolitlerde Güncel Bilgiler. STED 2005;14(1):5-7.
  • 23. Wang EE, Law BJ, Boucher FD, et al. Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of admission and management variation in patients hospitalized with respiratory syncytial viral lower respiratory tract infection. J Pediatr. 1996;129(3):390-5.
  • 24. Dahmer MK, O'cain P, Patwari PP, et al. The influence of genetic variation in surfactant protein B on severe lung injury in African American children. Crit Care Med. 2011;39(5):1138-44.
  • 25. Cao B, Bao Y, Liu C, Qi Q, Zhao Y, Yang F. A gene polymorphism at SP-B 1580 site regulates the pulmonary surfactant tension of viral pneumonia through the cellular pyroptosis signaling pathway. Am J Transl Res. 2023;15(12):6949-58.
  • 26. Steagall WK, Lin JP, Moss J. The C/A(-18) polymorphism in the surfactant protein B gene influences transcription and protein levels of surfactant protein B. Am J Physiol Lung Cell Mol Physiol. 2007;292(2):448-53.
  • 27. To KKW, Zhou J, Song YQ, et al. Surfactant protein B gene polymorphism is associated with severe influenza. Chest. 2014;145(6):1237-43.
  • 28. Cai BH, Chang LW, Li WB, et al. Association of surfactant protein B gene polymorphisms (C/A-18, C/T1580, intron 4 and A/G9306) and haplotypes with bronchopulmonary dysplasia in chinese han population. J Huazhong Univ Sci Technolog Med Sci. 2013;33(3):323-8.
  • 29. Floros J, Veletza SV, Kotikalapudi P, et al. Dinucleotide repeats in the human surfactant protein-B gene and respiratory-distress syndrome. Biochem J. 1995;305 (Pt 2)(Pt 2):583-90.
  • 30. Gerosa C, Fanni D, Cau F, et al. Immunohistochemical findings in the lungs of COVID-19 subjects: evidence of surfactant dysregulation. Eur Rev Med Pharmacol Sci. 2021;25(13):4639-43.
  • 31. Takahashi H, Sano H, Chiba H, Kuroki Y. Pulmonary surfactant proteins A and D: innate immune functions and biomarkers for lung diseases. Curr Pharm Des. 2006;12(5):589-98.
  • 32. McCormack FX, Whitsett JA. The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung. J Clin Invest. 2002;109(6):707-12.
  • 33. Leth-Larsen R, Garred P, Jensenius H, et al. A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D. J Immunol. 2005;174(3):1532-8.
  • 34. El Gayed E, Elhelbawy RH, Elhelbawy NG. Nicotinic acetylcholine receptors (rs1051730) gene polymorphism and surfactant protein D level in chronic obstructive pulmonary disease. Br J Biomed Sci. 2020;77(4):213-5.
  • 35. Floros J, Lin HM, García A, et al. Surfactant protein genetic marker alleles identify a subgroup of tuberculosis in a Mexican population. J Infect Dis. 2000;182(5):1473-8.
  • 36. El Saleeby CM, Li R, Somes GW, Dahmer MK, Quasney MW, DeVincenzo JP. Surfactant protein A2 polymorphisms and disease severity in a respiratory syncytial virus-infected population. J Pediatr. 2010;156(3):409-14.

Effect of Surfactant Protein B and D Genes Polymorphisms on Frequency and Severity of Acute Bronchiolitis

Yıl 2025, Cilt: 15 Sayı: 1, 1 - 5
https://doi.org/10.16899/jcm.1605226

Öz

Background and aim: Acute bronchiolitis (AB) is the most common cause of hospitalization in infants. Varying bronchiolitis presentations in patients with similar demographic characteristics suggest genetic causes of individual differences.
Materials and Methods: The study included 106 infants diagnosed with AB and 107 healthy infants recruited from a pediatric outpatient clinic. Genotyping was conducted for intron 4 and C/A–18 in the SP-B gene, along with SP-D/160 (Ala160Thr) and SP-D/270 (Ser270Thr) polymorphisms in the SP-D gene.
Results: The SP-B intron 4 invariant polymorphisms of ins/ins and ins/del were 93.40% and 4.72% in the AB group and 84.11% and 15.89% in the control group, respectively (p = 0.012). Frequency of polymorphism in the SP-D/270 (Ser270Thr) gene for Ser/Ser and Ser/Thr was 60% and 39.05% in the AB group and 79.44% and 18.69% in the control group, respectively (p = 0.004). The frequencies of Ser and Thr alleles were 79.90% and 20.10% in the AB group and 88.79% and 11.21% in the control group, respectively (p = 0.012). There was no observed correlation between the SP-B intron 4 and C/A-1, as well as the SP-D Ser270Thr and Ala160Thr polymorphisms, with the severity of AB (p > 0.05).
Conclusion: SP-B gene polymorphisms were identified as risk factors for AB, while SP-D polymorphisms appeared to play a protective role. However, these polymorphisms were not linked to AB severity. Early identification of children at risk could enable close monitoring and preventive care.

Etik Beyan

Gaziosmanpasa University Ethics Committee approval was received for this study (15-KAEK-040). The authors declare that they have no conflict of interest.

Destekleyen Kurum

This study was supported financially by Gaziosmanpasa University Scientific Research Projects Fund. Project number: 2014/53

Proje Numarası

2014/53

Teşekkür

We would like to thank PhD Osman Demir, assistant professor in Gaziosmanpasa University, Turkey, for his contribution to the statistical evaluation of the data of the study.

Kaynakça

  • 1. Bria M, Coates LEC. Wheezing in Infants: Bronchiolitis, in Nelson Textbook of Pediatrics, Kliegman RM, Editor. Elsevier: Canada. 2016;2044-50.
  • 2. Gul A, Takçı Ş, Altıntaş Seyyah B, Yılmaz R. Independent Predictorsof Severity and Hospitalization in Acute Bronchiolitis: Neutrophil/Lymphocyte Ratio and Mean Platelet Volume. J Pediatr Infect Dis2018;13(04):268-73.
  • 3. Yusen RD, Cohen AH, Hamvas A. Normal lung function in subjects heterozygous for surfactant protein-B deficiency. Am J Respir Crit Care Med. 1999;159(2):411-4.
  • 4. Tokieda K, Iwamoto HS, Bachurski C, et al. Surfactant protein-B-deficient mice are susceptible to hyperoxic lung injury. Am J Respir Cell Mol Biol. 1999;21(4):463-72.
  • 5. Tokieda K, Whitsett JA, Clark JC, et al. Pulmonary dysfunction in neonatal SP-B-deficient mice. Am J Physiol. 1997;273(4):875-82.
  • 6. Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol. 2005;5(1):58-68.
  • 7. Hamvas A. Inherited surfactant protein-B deficiency and surfactant protein-C associated disease: clinical features and evaluation. Semin Perinatol. 2006;30(6):316-26.
  • 8. Kültürsay N, Uygur Ö, Yalaz M. Yenidoğan döneminde sürfaktan kullanımı-bilinenler, halen araştırılanlar, araştırılması gerekenler. Türk Ped Arş 2014;49:1-12.
  • 9. Weaver TE, Whitsett JA. Function and regulation of expression of pulmonary surfactant-associated proteins. Biochem J. 1991;273(Pt 2)(Pt 2):249-64.
  • 10. Mallory GB Jr. Surfactant proteins: role in lung physiology and disease in early life. Paediatr Respir Rev. 2001;2(2):151-8.
  • 11. Cole FS, Hamvas A, Nogee LM. Genetic disorders of neonatal respiratory function. Pediatr Res. 2001;50(2):157-62.
  • 12. Ventre K, Haroon M, Davison C. Surfactant therapy for bronchiolitis in critically ill infants. Cochrane Database Syst Rev. 2006;(3):CD005150.
  • 13. Davison C, Ventre KM, Luchetti M, Randolph AG. Efficacy of interventions for bronchiolitis in critically ill infants: a systematic review and metaanalysis. Pediatr Crit Care Med. 2004;5(5):482-9.
  • 14. Hallman M, Haataja R. Surfactant protein polymorphisms and neonatal lung disease. Semin Perinatol. 2006;30(6):350-61.
  • 15. Sorensen GL. Surfactant Protein D in Respiratory and Non-Respiratory Diseases. Front Med (Lausanne). 2018;5:18.
  • 16. Hartshorn KL, Crouch E, White MR, et al. Pulmonary surfactant proteins A and D enhance neutrophil uptake of bacteria. Am J Physiol. 1998;274(6):958-69.
  • 17. LeVine AM, Elliott J, Whitsett JA, et al. Surfactant protein-d enhances phagocytosis and pulmonary clearance of respiratory syncytial virus. Am J Respir Cell Mol Biol. 2004;31(2):193-9.
  • 18. Pavlovic J, Papagaroufalis C, Xanthou M, et al. Genetic variants of surfactant proteins A, B, C, and D in bronchopulmonary dysplasia. Dis Markers. 2006;22(5-6):277-91.
  • 19. Leth-Larsen R, Garred P, Jensenius H, et al. A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D. J Immunol. 2005;174(3):1532-8.
  • 20. Lahti M, Lofgren J, Marttila R, et al. Surfactant protein D gene polymorphism associated with severe respiratory syncytial virus infection. Pediatr Res. 2002;51(6):696-9.
  • 21. Seyyah BA. The investigation of surfactant protein B and D gene polymorphism in infants with acute bronchiolitis, in Department of Pediatrics. Gaziosmanpasa University, Tokat Turkiye. 2016;72.
  • 22. Okutan Ö, Çeltik C. Akut Bronşiolitlerde Güncel Bilgiler. STED 2005;14(1):5-7.
  • 23. Wang EE, Law BJ, Boucher FD, et al. Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of admission and management variation in patients hospitalized with respiratory syncytial viral lower respiratory tract infection. J Pediatr. 1996;129(3):390-5.
  • 24. Dahmer MK, O'cain P, Patwari PP, et al. The influence of genetic variation in surfactant protein B on severe lung injury in African American children. Crit Care Med. 2011;39(5):1138-44.
  • 25. Cao B, Bao Y, Liu C, Qi Q, Zhao Y, Yang F. A gene polymorphism at SP-B 1580 site regulates the pulmonary surfactant tension of viral pneumonia through the cellular pyroptosis signaling pathway. Am J Transl Res. 2023;15(12):6949-58.
  • 26. Steagall WK, Lin JP, Moss J. The C/A(-18) polymorphism in the surfactant protein B gene influences transcription and protein levels of surfactant protein B. Am J Physiol Lung Cell Mol Physiol. 2007;292(2):448-53.
  • 27. To KKW, Zhou J, Song YQ, et al. Surfactant protein B gene polymorphism is associated with severe influenza. Chest. 2014;145(6):1237-43.
  • 28. Cai BH, Chang LW, Li WB, et al. Association of surfactant protein B gene polymorphisms (C/A-18, C/T1580, intron 4 and A/G9306) and haplotypes with bronchopulmonary dysplasia in chinese han population. J Huazhong Univ Sci Technolog Med Sci. 2013;33(3):323-8.
  • 29. Floros J, Veletza SV, Kotikalapudi P, et al. Dinucleotide repeats in the human surfactant protein-B gene and respiratory-distress syndrome. Biochem J. 1995;305 (Pt 2)(Pt 2):583-90.
  • 30. Gerosa C, Fanni D, Cau F, et al. Immunohistochemical findings in the lungs of COVID-19 subjects: evidence of surfactant dysregulation. Eur Rev Med Pharmacol Sci. 2021;25(13):4639-43.
  • 31. Takahashi H, Sano H, Chiba H, Kuroki Y. Pulmonary surfactant proteins A and D: innate immune functions and biomarkers for lung diseases. Curr Pharm Des. 2006;12(5):589-98.
  • 32. McCormack FX, Whitsett JA. The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung. J Clin Invest. 2002;109(6):707-12.
  • 33. Leth-Larsen R, Garred P, Jensenius H, et al. A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D. J Immunol. 2005;174(3):1532-8.
  • 34. El Gayed E, Elhelbawy RH, Elhelbawy NG. Nicotinic acetylcholine receptors (rs1051730) gene polymorphism and surfactant protein D level in chronic obstructive pulmonary disease. Br J Biomed Sci. 2020;77(4):213-5.
  • 35. Floros J, Lin HM, García A, et al. Surfactant protein genetic marker alleles identify a subgroup of tuberculosis in a Mexican population. J Infect Dis. 2000;182(5):1473-8.
  • 36. El Saleeby CM, Li R, Somes GW, Dahmer MK, Quasney MW, DeVincenzo JP. Surfactant protein A2 polymorphisms and disease severity in a respiratory syncytial virus-infected population. J Pediatr. 2010;156(3):409-14.
Toplam 36 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Çocuk Genetik Hastalıkları, Çocuk Göğüs Hastalıkları
Bölüm Orjinal Araştırma
Yazarlar

Buket Altıntaş Seyyah 0009-0006-3329-6604

Ali Gül 0000-0001-5350-2192

Şahin Takçı 0000-0001-9836-9727

Hacı Ömer Ateş 0000-0003-4266-393X

Resul Yılmaz 0000-0001-7672-8100

Proje Numarası 2014/53
Yayımlanma Tarihi
Gönderilme Tarihi 21 Aralık 2024
Kabul Tarihi 14 Ocak 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 15 Sayı: 1

Kaynak Göster

AMA Altıntaş Seyyah B, Gül A, Takçı Ş, Ateş HÖ, Yılmaz R. Effect of Surfactant Protein B and D Genes Polymorphisms on Frequency and Severity of Acute Bronchiolitis. J Contemp Med. 15(1):1-5. doi:10.16899/jcm.1605226