STAT6 Gene Polymorphisms in Allergic Rhinitis

  • Kim, Jeong Joong (Departments of Anatomy, and the Genomic Research Center for Immune Disorders, Wonkwang Institute of Medical Science, Wonkwang University School of Medicine) ;
  • Kim, Min Su (Departments of Anatomy, and the Genomic Research Center for Immune Disorders, Wonkwang Institute of Medical Science, Wonkwang University School of Medicine) ;
  • Lee, Jung Hun (Qtolaryngology, and the Genomic Research Center for Immune Disorders, Wonkwang Institute of Medical Science, Wonkwang University School of Medicine) ;
  • Choi, Tae Wook (Qtolaryngology, and the Genomic Research Center for Immune Disorders, Wonkwang Institute of Medical Science, Wonkwang University School of Medicine) ;
  • Choi, Sang Heon (Qtolaryngology, and the Genomic Research Center for Immune Disorders, Wonkwang Institute of Medical Science, Wonkwang University School of Medicine) ;
  • Lee, Jae Hoon (Qtolaryngology, and the Genomic Research Center for Immune Disorders, Wonkwang Institute of Medical Science, Wonkwang University School of Medicine) ;
  • Chung, Hun Taeg (Microbiology and Immunology, and the Genomic Research Center for Immune Disorders, Wonkwang Institute of Medical Science, Wonkwang University School of Medicine)
  • Published : 2004.09.01

Abstract

T helper-type 2 cytokines, such as IL-4 and IL-13, may play a central role in allergic diseases. The protein known as signal transducers and activators of transcription 6 (STAT6) is a key transcription factor involved in both IL-4- and -13-mediated biological responses. Two polymorphisms of the STAT 6 gene (exon 1 and G2964A variant) have been found. We investigated whether these STAT6 gene polymorph isms were associated with allergic rhinitis. Blood samples for genetic analysis were obtained from 285 individuals with allergic rhinitis and from 271 healthy subjects without atopic disease. The G2964A variant of the STAT6 gene was genotyped using PCR-RFLP analysis. The GT repeat polymorphism in exon 1 of the STAT6 gene was genotyped by fragment analysis. There was no association between the 2964A variant and GT repeat polymorphism in exon 1 of the STAT6 and allergic rhinitis in a Korean population (both p > 0.05). Our results suggest that a combination of STAT6 gene polymorphisms is not a useful marker for predicting allergic rhinitis.

Keywords

References

  1. Amoli, M., allier, W.E.R., and Hajeer, A.H. (2000). A novel PCR-RFLP assay for the detection of a polymorphism in the 3' of STAT6 gene. Genes Immun. 1, 349-350 https://doi.org/10.1038/sj.gene.6363684
  2. Bleecker, E.R. (1998). Mapping susceptibility genes for asthma allergy. Glin Exp Allergy 5, 6-12
  3. Callard, R.E., Matthews, D.J., and Hibbert, L.M. (1997). Interleukin 4 and interleukin 13: same response, different receptors. Biochem. Soc. Trans. 25,451-455 https://doi.org/10.1042/bst0250451
  4. Duetsch, G., Illig, T., Loesgen, S., Rohde, K., Klopp, N., Herbon, N., Gohlke, H., Altmueller, J., and Wjst, M (2002). STAT6 as an asthma candidate gene: polymorphismscreening, association and haplotype analysis in a Caucasian sib-pair study. Hum. Mol. Genet. 6, 613-621
  5. Edfors-Lubs, M (1971). Allergy in 7,000 twin pairs. Acta Allergol. 26, 249-285 https://doi.org/10.1111/j.1398-9995.1971.tb01300.x
  6. Gao, P.S., Mao, X.Q., Roberts, M.H., Arinobu, Y., Akaiwa, M., Enomoto, T., Dake, Y., Kawai, A., Sasaki, S., Hamasaki, N., Izuhara, K., Shirakawa, T., and Hopkin, J. M. (2000). Variants of STAT6 (signal transducer and activator of transcription 6) in atopic asthma. J. Med. Genet. 37, 380-382 https://doi.org/10.1136/jmg.37.5.380
  7. Howard, T.D., Whittaker, P.A., Zaiman, A.L., Koppelman, G.H., Xu, J., Hanley, M.T., Meyers, D.A., Postma, D.S., and Bleecker, E.R. (2001). Identification and association of polymorphisms in the interleukin-13 gene with asthma and atopy in a Dutch population. Am. J. Respir. Gell Mol. Biol. 25, 377-384 https://doi.org/10.1165/ajrcmb.25.3.4483
  8. Ihle, J.N. (1995). Cytokine receptor signaling. Nature 377, 591-594 https://doi.org/10.1038/377591a0
  9. Kapan, M.H., Schindler, U., Smiley, S.T., and Grusby, M.J. (1996). Stat6 is required for mediating responses to IL-4 and for the development of Th2 cells. Immunity. 4, 313-319 https://doi.org/10.1016/S1074-7613(00)80439-2
  10. Kim, J.J., Choi, T.W, Lee, J.H., Jang, C.H., Kim, Y.S., Chae, S.C., Chung, H.T., and Lee, J.H. (2004). Chemokine RANTES promoter polymorphisms in allergic rhinitis. Laryngoscope. 114,666-669 https://doi.org/10.1097/00005537-200404000-00013
  11. Kim, J.J., Kim, H.J., Lee, I.K., Chung, H.T., and Lee, J.H. (2004). Association between polymorphisms of the angiotensin-converting enzyme and angiotensinogen genes and allergic rhinitis in a Korean population. Ann. Otol. Rhinol. Laryngol.113, 297-302 https://doi.org/10.1177/000348940411300408
  12. Kruglyak, L. and Lickerson, D. A (2001). Variation is the spice of life. Nat Genet. 27, 234-236 https://doi.org/10.1038/85776
  13. Lee, J.H., Choi, T.W., Kim, J.J., Oh, C.K., Park, S.Y., Yoon, S.W, and Oh, G.J. (2004). Genetic susceptibilities of MCP-1 and CCR2 to the risk for Korean allergic rhinitis patients using polymorphism study. Korean J. Otolaryngol. 47, 127-131
  14. Lin, J.X., Migone, T.S., Tsang, M., Friedmann, M., Weatherbee, J.A., Zhou, L., Yamauchi, A, Bloom, E.T., Mietz, J., and John, S. (1995). The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15. Immunity 2, 331-339 https://doi.org/10.1016/1074-7613(95)90141-8
  15. Meyers, D.A., Postma, D.S., Panhuysen, C.I., Xu, J., Amelung, P.J., Levit, R.C., and Bleecker, E.R (1994). Evidence for a locus regulating total serum IgE levels mapping to chromosome 5. Genomics. 23, 464-470 https://doi.org/10.1006/geno.1994.1524
  16. Palmer, L.J., Burton, P.R., James, A.L., Musk, A.W., and Cookson, W.O. (2000). Familial aggregation and heritability of asthma-associated quantitative traits in a population-based sample of nuclear families. Eur. J. Hum Genet. 43, 30-37
  17. Patel, B.K., Keck, C.L., O'Leary, RS., Propescu, N.C., and LaRochelle, W. J. (1998). Localization of the human Stat6 gene to chromosome 12q13.3-q14.1, a region implicated in multiple solid tumors. Genomics. 52, 192-200 https://doi.org/10.1006/geno.1998.5436
  18. Shimoda, K., Sangster, M.Y., Sarawar, S.R., Sarawar, S.R., Carson, R.T., Tripp, R.A., Chu, C., Quelle, F.W., Nosaka, T., and Vignali, D.A.A. (1996). Lack of IL-4induced Th2 response and IgE class switching in mice with disrupted Stat6 gene. Nature 380, 630-633 https://doi.org/10.1038/380630a0
  19. Tamura, K., Arakawa, H, Suzuki, M., Kobayashi, H., Mochizuki, M, Tokuyama, K., and Morikawa, A. (2001). Novel dinucleotide repeat polymorphism in the first exon of the STAT6 gene is associated with allergic diseases. Glin. Exp. Allergy 31 , 1509-1514 https://doi.org/10.1046/j.1365-2222.2001.01191.x
  20. Tamura, K., Suzuki, M, Arakawa, H., Tokuyama, K., and Morikawa, A. (2003). Linkage and association studies of STAT6 gene polymorphisms and allergic Diseases. Int. Arch. Allergy Immunol.131 , 33-38 https://doi.org/10.1159/000070432
  21. Wilkinson, J., Thomas, N.S., Morton, N., and Holgate, S.T. (1999). Candidate gene and mutational analysis in asthma and atopy. Int. Arch. allergy Immunol. 118,265-267 https://doi.org/10.1159/000024095
  22. Yao, T., Kuo, M., See, L., Chen, L.G, Yan, D.C., Ou, L.S., Shaw, C.K., and Huang, J.L. (2003). The RANTES promoter polymorphism: A genetic risk factor for near-fatal asthma in Chinese children. J. Allergy Clin. Immunol. 111, 1285-92 https://doi.org/10.1067/mai.2003.1506