Mycoplasma pneumoniae 폐렴과 관련된 폐 표면 활성제 단백-A(Human Surfactant Protein-A) 유전자 대립 형질

Human Surfactant Protein-A(SP-A) Gene Locus Associated with Mycoplasma pneumoniae Pneumonia in Korean Children

  • 김승수 (순천향대학교 의과대학 소아과학교실) ;
  • 이인규 (순천향대학교 의과대학 소아과학교실) ;
  • 고정호 ;
  • 오명호 (순천향대학교 의과대학 소아과학교실) ;
  • 배종우 (경희대학교 의과대학 소아과학교실)
  • Kim, Seung Soo (Department of Pediatrics, College of Medicine, Soonchunhyang University) ;
  • Lee, In Kyu (Department of Pediatrics, College of Medicine, Soonchunhyang University) ;
  • Ko, Jung Ho (Protein Section, Laboratory of Metabolism(LM), National Cancer Institute(NCI), National Institute of Health(NIH)) ;
  • Oh, Myung Ho (Department of Pediatrics, College of Medicine, Soonchunhyang University) ;
  • Bae, Chong Woo (Department of Pediatrics, College of Medicine, Kyunghee University)
  • 투고 : 2004.10.07
  • 심사 : 2004.12.07
  • 발행 : 2005.04.15

초록

목 적 : 학동기에 많은 감염을 보이며 진단이 용이하고, 기관지 천식의 중요한 인자로 작용하는 M. pneumoniae 폐렴군과 숙주 방어에 중요하게 작용하는 SP-A를 중심으로 폐렴군과 대조군의 SP-A 유전자 대립 형질을 비교하여 M. pneumoniae 폐렴에 관여하는 유전자 대립 형질을 밝히고자 본 연구를 시행하였다. 방 법 : 2003년 5월부터 2003년 10월까지 순천향대학교 천안병원 소아과에 진찰 소견과 방사선 소견 상 폐렴으로 진단되어 입원한 환아 중, 최근 6개월간 폐렴의 병력이 없으며, M. pneumoniae 특이 항체 검사 상 항체가가 1 : 5,120 이상이거나, 회복기 항체가가 4배 이상 증가된 49례를 대상으로 하였으며, 순천향대학교 천안병원 신생아실에 입원한 정상 신생아 50명을 대조군으로 하여 아미노산 염기 서열의 차이에 의해 SP-A의 유전자형을 밝혔다. 결 과 : 1) 대조군에서 SP-A1 중 $6A^3$ 44.5%, $6A^2$ 28.7%, $6A^4$ 21.8%, 6A 1.1%의 분포를 보였고, SP-A2 중 $1A^0$ 40.7%, 1A 13.1%, $1A^5$ 11.4%, $1A^2$ 10%, $1A^1$ 9.3%의 분포를 보였다. 2) 폐렴군의 SP-A1 유전자 대립 형질은 대조군과 비교하여 통계적으로 유의한 차이가 없었다. 3) 폐렴군의 SP-A2 유전자 대립 형질 중 $1A^0$, $1A^1$ 그리고 $1A^5$는 대조군과 비교하여 낮은 빈도를 보였으나 통계적 의미는 없었으며, $1A^2$는 폐렴군에서 통계적으로 유의하게 높은 분포를 보였다. 결 론 : M. pneumoniae 폐렴에 대해 $1A^2$는 유발 인자로 작용할 것으로 추정할 수 있으며, $1A^2$에 대한 단백질의 정량, 정성분석을 통하여 M. pneumoniae의 예방이나 치료에 어떻게 적용할 것인지 연구되어야 한다고 생각된다.

Purpose : Mycoplasama pneumoniae is a leading cause of pneumonia and exacerbates other respiratory conditions such as asthma. Surfactant protein A(SP-A) is involved in surfactant physiology and surfactant structure, and plays a major role in innate host defense and inflammatory processes in the lung. In this study, SP-A mediated mycoplasma cidal activity. The candidate-gene approach was used to study the association between the SP-A gene locus and Mycoplasama pneumoniae pneumonia in the genetically homogeneous Korean population. Methods : PCR-cRFLP-based methodology was used to detect SP-A genotype. The forty nine children with Mycoplasama pneumoniae pneumonia were matched to 50 nomal neonates. Results : The specific frequencies for the alleles of the SP-A1 and SP-A2 gene in the study population were : $6A^2=21$ percent, $6A^3=45$ percent, $6A^4=11$ percent, $6A^8=9$ percent, $6A^{14}=8$ percent, 1A=11.3 percent, $1A^0=38$ percent, $1A^1=12.7$ percent, $1A^2=9.2$ percent, $1A^5=15.5$ percent, $1A^7=2.9$ percent, $1A^8=4.9$ percent, $1A^9=2.2$ percent, others=3.3 percent. The frequencies of specific genotypes such as $1A^2$ was higher than control group, significantly. Conclusion : $1A^2$ are susceptible factors for Mycoplasama pneumoniae pneumonia. We conclude that the SP-A gene locus($1A^2$) is an important determinant for predisposition to Mycoplasama pneumoniae pneumonia in children.

키워드

과제정보

연구 과제 주관 기관 : 순천향대학교

참고문헌

  1. Drickamer K. Demonstration of carbohydrate-recognition activity in diverse proteins which share a common primary structure modif. Biochem Soc Trans 1989;17:13-5
  2. LeVine AM, Bruno MD, Huelsman KM, Ross GF, Whitsett JA, Korfhagen TR. Surfactant protein A-deficient mice are susceptible to group B streptococcal infection. J Immunol 1997;158:4336-40
  3. Phelps DS. Pulmonary surfactant modulation of host-defense function. Appl Cardiopulm Pathophysiol 1995;5:221-9
  4. Hickman-Davis JM, Russell LJ, Zhu S, Matalon S. Surfactant protein A mediates mycoplasmacidal activity of alveolar macrophages. Am J Physiol 1998;274:L270-7
  5. Chiba H, Pattanajitvilai S, Mitsuzawa H, Kuroki Y, Evans A, Voelker DR. Pulmonary surfactant proteins A and D recognize lipid ligands on Mycoplasma pneumoniae and markedly augment the innate immune response to the organism organism. Chest 2003;123(3 suppl):426s https://doi.org/10.1378/chest.123.3_suppl.426S
  6. Krause DC, Taylor-Robinson D. Mycoplasmas which infect humans. In : Maniloff J, McElhaney RN, editors. Mycoplasmas : molecular biology and pathogenesis. Washington, DC : American Society for Microbiology, 1992:417-44
  7. Gil JC, Cedillo RC, Mayagoitia BG, Paz MD. Isolation of Mycoplasma pneumoniae from asthmatic patients. Ann Allergy 1993;70:23-5
  8. Melbye H, Kongerud J, Vorland L. Reversible airflow limitation in adults with respiratory infection. Eur Respir J 1994;7:1239-45 https://doi.org/10.1183/09031936.94.07071239
  9. DiAngelo S, Lin Z, Wang G, Phillips S, Ramet M, Luo J, et al. Novel, non-radioactive, simple and multiplex PCRcRFLP methods for genotyping human SP-A and SP-D marker alleles. Dis Markers 1999;15:269-81
  10. Davis JK, Davidson MK, Schoeb TR, Lindsey JR. Decreased intrapulmonary killing of Mycoplasma pulmonis after short-term exposure to NO2 is associated with damaged alveolar macrophages. Am Rev Respir Dis 1992;145: 406-11 https://doi.org/10.1164/ajrccm/145.2_Pt_1.406
  11. Evengard B, Sandstedt K, Bolske G, Feinstein R, Riesenfelt-Orn I, Smith CI. Intranasal inoculation of Mycoplasma pulmonis in mice with severe combined immunodeficiency (SCID) causes a wasting disease with grave arthritis. Clin Exp Immunol 1994;98:388-94
  12. Foy HM. Infections caused by Mycoplasma pneumoniae and possible carrier state in different populations of patients. Clin Infect Dis 1993;17 Suppl 1:S37-46
  13. Lo SC. Mycoplasmas and AIDS. In : Maniloff J, McElhaney RN, editors. mycoplasmas : molecular biology and pathogenesis. Washington, DC : American Society for Microbiology, 1992:525-45
  14. Lee KS, Kim YH, Suk JS, Ko JH, Yoo OJ, Lee IK, et al. Allele distribution and frequency of human surfactant protein-A1 in Korean neonates. J Korean Pediatr Soc 2002;45: 1497-502
  15. Kim NC, Yoon HC, Suk JS, Ko JH, Yoo OJ, Lee IK, et al. Allele distribution and frequency of human surfactant protein-A2 in Korean neonates. J Korean Pediatr Soc 2003;46: 340-4
  16. Ramet M, Haataja R, Marttila R, Floros J, Hallman M. Association between the surfactant protein A(SP-A) gene locus and respiratory distress syndrome in the Finnish population. Am J Hum Genet 2000;66:1569-79 https://doi.org/10.1086/302906
  17. Floros J, Fan R, Matthews A, DiAngelo S, Luo J, Nielsen H, et al. Family-based transmission disequilibrium test (TDT) and case-control association studies reveal surfactant protein A(SP-A) susceptibility alleles for respiratory distress syndrome(RDS) and possible race differences. Clin Genet 2001;60:178-87 https://doi.org/10.1034/j.1399-0004.2001.600303.x
  18. Choe JH, Oh MH, Ko JH, Lee IK, Kim SY, Bae CW. Association between the human surfactant protein-A(SP-A) gene locus and respiratory distress syndrome in the korean neonates. Korean J Pediatr 2004;47:735-9