대한의생명과학회지 (Biomedical Science Letters)

  • 제26권4호
  • /
  • Pages.344-350
  • /
  • 2020
  • /
  • 1738-3226(pISSN)
  • /
  • 2288-7415(eISSN)
대한의생명과학회 (The Korean Society for Biomedical Laboratory Sciences)
권호 표지
DOI QR코드

DOI QR Code

Association of Single Nucleotide Polymorphisms in Interleukin-12 Receptor (IL-12Rβ1 and IL-12Rβ2) with Asthma in a Korean Population

  • Jung, Jaemee (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University) ;
  • Park, Sangjung (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University) ;
  • Kim, Sung-Soo (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University) ;
  • Hong, Mijin (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University) ;
  • Choi, Eunhye (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University) ;
  • Jin, Hyun-Seok (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University) ;
  • Hwang, Dahyun (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University)
  • 투고 : 2020.12.01
  • 심사 : 2020.12.16
  • 발행 : 2020.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Asthma is a chronic disease and occurs in airway in the lung. The cause of the disease has not been identified, it is assumed that both genetic and environmental risk factors play an important role in the development of asthma. Interleukin (IL)-12 is a cytokine regulating T-cell and NK cell. In this study, we analyzed the genetic polymorphisms of IL-12 receptor genes (IL-12Rβ1 and IL-12Rβ2) in asthma patients and normal individuals in a Korean population. We analyzed single nucleotide polymorphisms (SNPs) in IL-12Rβ1 and IL-12Rβ2 using the genotype data of 193 asthma cases and 3,228 healthy controls from the Korea Association REsource for their correlation with asthma case. IL-12Rβ1 and IL-12Rβ2 genes showed statistically significant polymorphism association with asthma case. As a results, 16 SNPs from IL-12Rβ1 and IL-12Rβ2 genes showed statistically significant association with asthma. Among them, rs375947 SNP in IL-12Rβ1 showed the greatest statistical correlation with asthma (P-value = 0.028, Odds Ratio = 1.27, 95% Confidence Interval = 1.03~1.57). The groups with minor allele of IL-12Rβ1 and IL-12Rβ2 showed increased risk of asthma. The genotype-based mRNA expression analysis showed that the group of minor allele of IL-12Rβ1 showed decreased mRNA expression. Decreased IL-12Rβ1 expression causes decreased IL-12 signaling, and this affects developing asthma. In conclusion, the SNPs in IL-12Rβ1 and IL-12Rβ2 may contribute to development of asthma in a Korean population.

키워드

참고문헌

  1. Asher MI, Montefort S, Bjorksten B, Lai CK, Strachan DP, Weiland SK, Williams H, ISAAC Phase Three Study Group. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. The Lancet. 2006. 368: 733-743. https://doi.org/10.1016/S0140-6736(06)69283-0
  2. Backman H, Raisanen P, Hedman L, Stridsman C, Andersson M, Lindberg A, Lundback B, Ronmark E. Increased prevalence of allergic asthma from 1996 to 2006 and further to 2016-results from three population surveys. Clin Exp Allergy. 2017. 47: 1426-1435. https://doi.org/10.1111/cea.12963
  3. Chang Y. Practical guideline of asthma management-Korean guideline for asthma 2015-. Korean J Med. 2016. 90: 298-306. https://doi.org/10.3904/kjm.2016.90.4.298
  4. Chen T, Liang W, Gao L, Wang Y, Liu Y, Zhang L, Zhang L. Association of single nucleotide polymorphisms in interleukin 12 (IL-12A and-B) with asthma in a Chinese population. Hum Immunol. 2011. 72: 603-606. https://doi.org/10.1016/j.humimm.2011.03.018
  5. Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, Ban H, Yoon D, Lee MH, Kim D, Park M. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet. 2009. 41: 527-534. https://doi.org/10.1038/ng.357
  6. Chung F. Anti-inflammatory cytokines in asthma and allergy: interleukin-10, interleukin-12, interferon-γ. Mediators Inflamm. 2001. 10: 51-59. https://doi.org/10.1080/09629350120054518
  7. Gately MK, Renzetti LM, Magram J, Stern AS, Adorini L, Gubler U, Presky DH. The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu Rev Immunol. 1998. 16: 495-521. https://doi.org/10.1146/annurev.immunol.16.1.495
  8. Hirota T, Suzuki Y, Hasegawa K, Obara K, Matsuda A, Akahoshi M, Nakashima K, Cheng L, Takahashi N, Shimizu M, Doi S, Fujita K, Enomoto T, Ebisawa M, Yoshihara S, Nakamura Y, Kishi F, Shirakawa T, Tamari M. Functional haplotypes of IL-12B are associated with childhood atopic asthma. J Allergy Clin Immunol. 2005. 116: 789-795. https://doi.org/10.1016/j.jaci.2005.06.010
  9. Hsieh C, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM. Development of TH1 CD4 T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993. 260: 547-549. https://doi.org/10.1126/science.8097338
  10. International HapMap Consortium. The International HapMap Project. Nature. 2003. 426: 789-796. https://doi.org/10.1038/nature02168
  11. Leonard P, Sur S. Interleukin-12. BioDrugs. 2003. 17: 1-7. https://doi.org/10.2165/00063030-200317010-00001
  12. Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol. 2010. 34: 816-834. https://doi.org/10.1002/gepi.20533
  13. Litjens NH, Van Der Plas, Mariena JA, Ravensbergen B, NumanRuberg SC, Van Assen Y, Thio HB, Van Dissel JT, van de Vosse E, Nibbering PH. Psoriasis is not associated with IL-12p70/IL-12p40 production and IL12B promoter polymorphism. J Invest Dermatol. 2004. 122: 923-926. https://doi.org/10.1111/j.0022-202X.2004.22427.x
  14. Mo JH. T cell differentiation and Th17. Korean J Otorhinolaryngol-Head Neck Surg. 2008. 51: 688-693. https://doi.org/10.3342/kjorl-hns.2008.51.8.688
  15. Park CS. Genetics of Branchal Asthma. Tuberc Respir Dis. 2006. 60: 391-396. https://doi.org/10.4046/trd.2006.60.4.391
  16. Presky DH, Yang H, Minetti LJ, Chua AO, Nabavi N, Wu C, Gately MK, Gubler U. A functional interleukin 12 receptor complex is composed of two β-type cytokine receptor subunits. Proc Natl Acad Sci. 1996. 93: 14002-14007. https://doi.org/10.1073/pnas.93.24.14002
  17. Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, Boehnke M, Abecasis GR, Willer CJ. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics. 2010. 26: 2336-2337. https://doi.org/10.1093/bioinformatics/btq419
  18. Shen T, Tsai C, Chang W, Wang S, Chao C, Hsiao C, Chen W, Hsia T, Bau D. Association of interleukin-12A rs568408 with susceptibility to asthma in Taiwan. Sci Rep. 2017. 7: 1-7. https://doi.org/10.1038/s41598-016-0028-x
  19. Steinke JW, Rich SS, Borish L. Genetics of allergic disease. J Allergy Clin Immunol. 2008. 121: S384-S387. https://doi.org/10.1016/j.jaci.2007.07.029
  20. To T, Stanojevic S, Moores G, Gershon AS, Bateman ED, Cruz AA, Boulet L. Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health. 2012. 12: 204. https://doi.org/10.1186/1471-2458-12-204
  21. Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol. 2003. 3: 133-146. https://doi.org/10.1038/nri1001
  22. van de Vosse E, Haverkamp MH, Ramirez-Alejo N, Martinez-Gallo M, Blancas-Galicia L, Metin A, Garty BZ, Sun-Tan C, Broides A, de Paus RA. IL12Rβ1 Deficiency: Mutation Update and Description of the IL12RB1 Variation Database. Hum Mutat. 2013. 34: 1329-1339. https://doi.org/10.1002/humu.22380