DOI QR코드

DOI QR Code

사람의 IL-27p28 유전자 다형성은 알레르기성 비염 환자 혈청의 IgE 양과 연관됨

Human IL-27p28 Gene Polymorphisms are Associated with the Serum Total IgE Levels of Allergic Rhinitis Patients

  • 유지인 (원광대학교 의과대학 병리학교실) ;
  • 한원철 (원광대학교 의과대학 병리학교실) ;
  • 이재훈 (원광대학교 의과대학 이비인후과학교실) ;
  • 김헌수 (원광대학교 의과대학 병리학교실) ;
  • 윤기중 (원광대학교 의과대학 소화기질환연구소) ;
  • 이재훈 (원광대학교 의과대학 내과학교실) ;
  • 문형배 (원광대학교 의과대학 병리학교실) ;
  • 채수천 (원광대학교 의과대학 병리학교실)
  • Yu, Ji-In (Department of Pathology, Wonkwang University School of Medicine) ;
  • Han, Weon-Cheol (Department of Pathology, Wonkwang University School of Medicine) ;
  • Lee, Jae-Hoon (Department of Otolaryngology, Wonkwang University School of Medicine) ;
  • Kim, Hun-Soo (Department of Pathology, Wonkwang University School of Medicine) ;
  • Yun, Ki-Jung (Digestive Disease Research Institute, Wonkwang University School of Medicine) ;
  • Lee, Jae-Hoon (Department of Internal Medicine, Wonkwang University School of Medicine) ;
  • Moon, Hyung-Bae (Department of Pathology, Wonkwang University School of Medicine) ;
  • Chae, Soo-Cheon (Department of Pathology, Wonkwang University School of Medicine)
  • 발행 : 2009.03.31

초록

인터루킨 27(IL-27)은 인터루킨 12계열의 이성이량체 사이토카인으로 EBI3와 p28의 두 서브유니트로 구성 되어 있다. 인터루킨 27은 Th1 개시의 초기 조절에 관여하는 사이토카인으로 Th2 인자인 GATA-3의 작용을 억제하는 역할을 한다. 이 사이토카인은 $CD4^+$ T 림프구와 자연살해세포에서 아주 높게 발현하는 수용체(WSX-1)에 의하여 매개된다. 우리들은 사람의 IL-27p28유전자에서 네 개의 유전자다형성 부위를 찾아서 이들 유전자다형성이 기관지 천식의 감수성에 영향을 미치는 것을 보고한 바 있다. 이 연구에서는 IL-27p28 유전자의 유전자다형성이 알레르기성 비염의 감수성에 영향을 미치는 지를 알아보기 위하여 이들 다형성에 있어서 알레르기성 비염환자 군과 정상인군 사이의 유전자형 및 대립형질의 빈도를 비교분석 하였다. 비록 알레르기성 비염환자 군에서 IL-27p28 유전자의 유전자다형성의 유전자형 및 대립형질의 빈도의 차는 정상인 군의 그것과 큰 차이가 없었으나, g.2905T>G SNP에서 두 그룹간에 주목할만한 차이(P=0.037)를 발견하였다. 이 결과는 IL-27p28 유전자의 g.2905T>G 유전자 형성이 알레르기성 비염환자에서 IgE의 생산에 영향을 준다는 것을 암시한다.

Interleukin 27 (IL-27) was discovered as a heterodimeric cytokine of the IL-12 family, and is composed of two subunits - Epstein-Barr virus induced gene 3 (EBI3) and p28. It acts as a versatile cytokine in the early regulation of Th1 initiation and in the negative regulation of the Th2 factor GATA binding protein 3 (GATA-3). This cytokine is mediated by the IL-27 receptor (WSX-1), which is highly expressed on $CD4^+$ T lymphocytes and NK cells. We previously identified four polymorphisms in the human IL-27p28 gene and suggested that the polymorphism of IL-27p28 is associated with susceptibility to asthma. To determine whether these IL-27p28 SNPs are associated with susceptibility to allergic rhinitis, the genotype and allele frequencies of IL-27p28 SNPs were analyzed between allergic rhinitis patients and healthy controls. Although the genotype and allele frequencies of IL-27p28 SNPs in allergic rhinitis patients were not significantly different from those of the control group, there was a suggestive difference (P=0.037) between these groups in total serum IgE levels in the g.2905T>G SNP of the IL-27p28 gene. Our result implies that the g.2905T>G SNP of the IL-27p28 gene might have an affect on IgE production in allergic rhinitis patients.

키워드

참고문헌

  1. Chae, S. C., C. S. Li, K. M. Kim, J. Y. Yang, Q. Zhang, Y. C. Lee, Y. S. Yang, and H. T. Chung. 2007. Identification of polymorphisms in human interleukin-27 and their association with asthma in a Korean population. J. Hum. Genet. 52, 355-361 https://doi.org/10.1007/s10038-007-0123-8
  2. Chae, S. C., Y. R. Park, G. J. Oh, J. H. Lee, and H. T. Chung. 2005. The suggestive association of eotaxin-2 and eotaxin-3 gene polymorphisms in Korean population with allergic rhinitis. Immunogenetics 56, 760-764 https://doi.org/10.1007/s00251-004-0746-2
  3. Chae, S. C., Y. R. Park, J. H. Song, S. C. Shim, K. S. Yoon, and H. T. Chung. 2005. The polymorphisms of Tim-1 promoter region are associated with rheumatoid arthritis in a Korean population. Immunogenetics 56, 696-701 https://doi.org/10.1007/s00251-004-0743-5
  4. Chae, S. C., Y. R. Park, S. C. Li, J. H. Lee, Y. S. Yang, Q. Zhang, K. S. Kim, and H. T. Chung. 2006. Analysis of the variations in IL-28RA gene and their association with allergic rhinitis. Exp. Mol. Med. 38, 302-309 https://doi.org/10.1038/emm.2006.36
  5. Cheng, L., T. Enomoto, T. Hirota, M. Shimizu, N. Takahashi, M. Akahoshi, A. Matsuda, Y. Dake, S. Doi, K. Enomoto, A. Yamasaki, S. Fukuda, X. Q. Mao, J. M. Hopkin, M. Tamari, and T. Shirakawa. 2004. Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen. Clin. Exp. Allergy. 34, 1192-1201 https://doi.org/10.1111/j.1365-2222.2004.02008.x
  6. Daser, A., N. Meissner, U. Herz, and H. Renz. 1995. Role and modulation of T-cell cytokines in allergy. Curr. Opin. Immunol. 28, 762-770 https://doi.org/10.1016/0952-7915(95)80045-X
  7. Devergne, O., M. Hummel, H. Koeppen, M. M. Le Beau, E. C. Nathanson, E. Kieff, and M. Birkenbach. 1996. A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes. J. Virol. 70, 1143-1153
  8. Hofstra, C. L., I. Van Ark, G. Hofman, M. Kool, F. P. Nijkamp, and A. J. Van Oosterhout. 1998. Prevention of Th2-like cells responses by coadministration of IL-12 and IL-18 is associated with inhibition of antigen-induced airway hyperresponsiveness, eosinophilia, and serum IgE levels. J. Immunol. 161, 5054-5060 https://doi.org/10.1046/j.1365-2249.2003.02073.x
  9. Ho, I. C. and L. H. Glimcher. 2002. Transcription: Tantalizing Times for T Cells. Cell 109, S109-120 https://doi.org/10.1016/S0092-8674(02)00705-5
  10. Li, C. S., S. C. Chae, J. H. Lee, Q. Zhang, and H. T. Chung. 2006. Identification of single nucleotide polymorphisms in FOXJ1 and their association with allergic rhinitis. J. Hum. Genet. 51, 292-297 https://doi.org/10.1007/s10038-006-0359-8
  11. Miyazaki, Y., H. Inoue, M. Matsumura, K. Matsumoto, T. Nakano, M. Tsuda, S. Hamano, A. Yoshimura, and H. Yoshida. 2005. Exacerbation of experimental allergic asthma by augmented Th2 responses in WSX-1-deficient mice. J. Immunol. 175, 2401-2407 https://doi.org/10.4049/jimmunol.175.4.2401
  12. O'Garra, A. 1998. Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 8, 275-283 https://doi.org/10.1016/S1074-7613(00)80533-6
  13. Passali, D., M. Lauriello, C. Mezzedimi, G. C. Passali, and L. Bellussi. 2001. Natural history of allergic rhinitis a review. Clin. Applied. Immunol. Rev. 1, 207-216 https://doi.org/10.1016/S1529-1049(01)00016-2
  14. Pflanz, S., J. C. Timans, J. Cheung, R. Rosales, H. Kanzler, J. Gilbert, L. Hibbert, T. Churakova, M. Travis, E. Vaisberg, W. M. Blumenschein, J. D. Mattson, J. L. Wagner, W. To, S. Zurawski, T. K. McClanahan, D. M. Gorman, J. F. Bazan, R. de Waal Malefyt, D. Rennick, and R. A. Kastelein. 2002. IL-27, a heterodimeric cytokine composed of EBIS and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity 16, 779-790 https://doi.org/10.1016/S1074-7613(02)00324-2
  15. Pflanz, S., L. Hibbert, J. Mattson, R. Rosales, E. Vaisberg, J. F. Bazan, J. H. Phillips, T. K. McClanahan, R. de Waal Malefyt, and R. A. Kastelein. 2004. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J. Immunol. 172, 2225-2231 https://doi.org/10.1073/pnas.242603899.PMID12477932
  16. Sprecher, C. A., F. J. Grant, J. W. Baumgartner, S. R. Presnell, S. K. Schrader, T. Yamagiwa, T. E. Whitmore, P. J. O'Hara, and D. F. Foster. 1998. Cloning and characterization of a novel class I cytokine receptor. Biochem. Biophys. Res. Commun. 246, 82-90 https://doi.org/10.1006/bbrc.1998.8576
  17. Wang, M., Z. M. Xing, C. Lu, Y. X. Ma, D. L. Yu, Z. Yan, S. W. Wang, and L. S. Yu. 2003. A common IL-13 Arg130Gln single nucleotide polymorphism among Chinese atopy patients with allergic rhinitis. Hum. Genet. 113, 387-390 https://doi.org/10.1007/s00439-003-1001-x