The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

A polymorphism in the histone deacetylase 1 gene is associated with the response to corticosteroids in asthmatics

  • Kim, Min-Hye (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Kim, Sae-Hoon (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Kim, Yook-Keun (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Hong, Soo-Jong (Department of Pediatrics, Childhood Asthma Atopy Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Min, Kyung-Up (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Cho, Sang-Heon (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Park, Heung-Woo (Department of Internal Medicine, Seoul National University College of Medicine)
  • Received : 2013.03.22
  • Accepted : 2013.06.12
  • Published : 2013.11.01
⟨ Previous Next ⟩

Abstract

Background/Aims: Recent investigations suggest that histone deacetylase 1 (HDAC1) and HDAC2 may be target molecules to predict therapeutic responses to corticosteroids. We evaluated the effects of variation in HDAC1 and HDAC2 on the response to corticosteroids in asthmatics. Methods: Two single nucleotide polymorphisms (SNPs) were selected after resequencing HDAC1 and HDAC2. For the first analysis, we evaluated the association between those SNPs and asthma severity in 477 asthmatics. For the second analysis, we evaluated the effects of these SNPs on lung function improvements in response to corticosteroid treatment in 35 independent adult asthmatics and 70 childhood asthmatics. Results: We found that one SNP in HDAC1 (rs1741981) was significantly related to asthma severity in a recessive model (corrected p = 0.036). Adult asthmatics who were homozygous for the minor allele of rs1741981 showed significantly lower % forced expiratory volume in 1 second ($%FEV_1$) increases in response to systemic corticosteroids treatment compared with the heterozygotes or those homozygous for the major allele ($12.7%{\pm}7.2%$ vs. $37.4%{\pm}33.7%$, p = 0.018). Similarly, childhood asthmatics who were homozygous for the minor allele of rs1741981 showed significantly lower $%FEV_1$ increases in response to inhaled corticosteroid treatment compared with the heterozygotes or those homozygous for the major allele ($14.1%{\pm}5.9%$ vs. $19.4%{\pm}8.9%$, p = 0.035). Conclusions: The present study demonstrated that rs1741981 in $HDAC_1$ was significantly associated with the response to corticosteroid treatment in asthmatics.

Keywords

References

  1. Bahadori K, Doyle-Waters MM, Marra C, et al. Economic burden of asthma: a systematic review. BMC Pulm Med 2009;9:24. https://doi.org/10.1186/1471-2466-9-24
  2. The Global Initiative for Asthma. The guideline for asthma management and prevention 2010 [Internet]. [place unknown]: The Global Initiative for Asthma [cited 2013 Jan 28]. Available from: http://www.ginasthma.org/guidelines-pocket-guide-for-asthma-management.html.
  3. National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma full report 2007 [Internet]. Bethesda (MD): The National Heart, Lung, and Blood Institute (NHLBI) Health Information Center, 2007 [cited 2013 Jan 28]. Available from http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
  4. British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma [Internet]. London: British Thoracic Society, 2012 [cited 2013 Jan 28]. Available from http://www.sign.ac.uk/pdf/sign101.pdf.
  5. Inglis GC, Ingram MC, Holloway CD, et al. Familial pattern of corticosteroids and their metabolism in adult human subjects: the Scottish Adult Twin Study. J Clin Endocrinol Metab 1999;84:4132-4137.
  6. Ober C, Abney M, McPeek MS. The genetic dissection of complex traits in a founder population. Am J Hum Genet 2001;69:1068-1079. https://doi.org/10.1086/324025
  7. Schwartz JT, Reuling FH, Feinleib M, Garrison RJ, Collie DJ. Twin heritability study of the effect of corticosteroids on intraocular pressure. J Med Genet 1972;9:137-143. https://doi.org/10.1136/jmg.9.2.137
  8. Drazen JM, Silverman EK, Lee TH. Heterogeneity of therapeutic responses in asthma. Br Med Bull 2000;56:1054-1070. https://doi.org/10.1258/0007142001903535
  9. Adcock IM, Ford P, Ito K, Barnes PJ. Epigenetics and airways disease. Respir Res 2006;7:21. https://doi.org/10.1186/1465-9921-7-21
  10. Bhavsar P, Ahmad T, Adcock IM. The role of histone deacetylases in asthma and allergic diseases. J Allergy Clin Immunol 2008;121:580-584.
  11. Grausenburger R, Bilic I, Boucheron N, et al. Conditional deletion of histone deacetylase 1 in T cells leads to enhanced airway inf lammation and increased Th2 cytokine production. J Immunol 2010;185:3489-3497. https://doi.org/10.4049/jimmunol.0903610
  12. Barnes PJ, Ito K, Adcock IM. Corticosteroid resistance in chronic obstructive pulmonary disease: inactivation of histone deacetylase. Lancet 2004;363:731-733. https://doi.org/10.1016/S0140-6736(04)15650-X
  13. Barnes PJ. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol 2013;131:636-645.
  14. Boulet LP, Becker A, Berube D, Beveridge R, Ernst P; The Canadian Asthma Consensus Group. Canadian asthma consensus report, 1999. Can Med Assoc J 1999;161(11 Suppl 1):S1-S5.
  15. Ungar WJ, Chapman KR, Santos MT. Assessment of a medication-based asthma index for population research. Am J Respir Crit Care Med 2002;165:190-194. https://doi.org/10.1164/ajrccm.165.2.2102012
  16. Park HW, Shin ES, Lee JE, et al. Association between genetic variations in prostaglandin E2 receptor subtype EP3 gene (Ptger3) and asthma in the Korean population. Clin Exp Allergy 2007;37:1609-1615. https://doi.org/10.1111/j.1365-2222.2007.02820.x
  17. Park HW, Lee JE, Shin ES, et al. Association between genetic variations of vascular endothelial growth factor receptor 2 and atopy in the Korean population. J Allergy Clin Immunol 2006;117:774-779.
  18. Stouffer SA, Suchman EA, DeVinney LC, et al. Studies in social psychology in World War II. Vol 1. The American Soldier: Adjustment during Army Life. Princeton: Princeton University Press, 1949.
  19. Barnes PJ. How corticosteroids control inf lammation: Quintiles Prize Lecture 2005. Br J Pharmacol 2006;148:245-254.
  20. 20. Barnes PJ, Adcock IM. Glucocorticoid resistance in inflammatory diseases. Lancet 2009;373:1905-1917. https://doi.org/10.1016/S0140-6736(09)60326-3
  21. Ito K, Caramori G, Lim S, et al. Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med 2002;166:392-396. https://doi.org/10.1164/rccm.2110060
  22. Ito K, Yamamura S, Essilf ie-Quaye S, et al. Histone deacetylase 2-mediated deacetylation of the glucocorticoid receptor enables NF-kappaB suppression. J Exp Med 2006;203:7-13. https://doi.org/10.1084/jem.20050466
  23. Corrigan CJ, Brown PH, Barnes NC, et al. Glucocorticoid resistance in chronic asthma: glucocorticoid pharmacokinetics, glucocorticoid receptor characteristics, and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro. Am Rev Respir Dis 1991;144:1016-1025. https://doi.org/10.1164/ajrccm/144.5.1016
  24. Haczku A, Alexander A, Brown P, et al. The effect of dexamethasone, cyclosporine, and rapamycin on T-lymphocyte proliferation in vitro: comparison of cells from patients with glucocorticoid-sensitive and glucocorticoid-resistant chronic asthma. J Allergy Clin Immunol 1994;93:510-519.
  25. Spahn JD, Landwehr LP, Nimmagadda S, Surs W, Leung DY, Szefler SJ. Effects of glucocorticoids on lymphocyte activation in patients with steroid-sensitive and steroid-resistant asthma. J Allergy Clin Immunol 1996;98(6 Pt 1):1073-1079.
  26. Choi JH, Oh SW, Kang MS, Kwon HJ, Oh GT, Kim DY. Trichostatin A attenuates airway inf lammation in mouse asthma model. Clin Exp Allergy 2005;35:89-96. https://doi.org/10.1111/j.1365-2222.2004.02006.x
  27. Lee PH, Shatkay H. F-SNP: computationally predicted functional SNPs for disease association studies. Nucleic Acids Res 2008;36(Database issue):D820-D824.
  28. Heinemeyer T, Wingender E, Reuter I, et al. Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL. Nucleic Acids Res 1998;26:362-367. https://doi.org/10.1093/nar/26.1.362
  29. Sandelin A, Wasserman WW, Lenhard B. ConSite: webbased prediction of regulatory elements using cross-species comparison. Nucleic Acids Res 2004;32(Web Server issue):W249-W252. https://doi.org/10.1093/nar/gkh372
  30. Lee PH, Shatkay H. An integrative scoring system for ranking SNPs by their potential deleterious effects. Bioinformatics 2009;25:1048-1055. https://doi.org/10.1093/bioinformatics/btp103
  31. Lima JJ, Holbrook JT, Wang J, et al. The C523A beta2 adrenergic receptor polymorphism associates with markers of asthma severity in African Americans. J Asthma 2006;43:185-191. https://doi.org/10.1080/02770900600566611

Cited by

  1. Trek1 contributes to maintaining nasal epithelial barrier integrity vol.5, pp.None, 2013, https://doi.org/10.1038/srep09191
  2. Association between TAAR6 polymorphisms and airway responsiveness to inhaled corticosteroids in asthmatic patients vol.25, pp.7, 2013, https://doi.org/10.1097/fpc.0000000000000141
  3. Effects of genetic factors to inhaled corticosteroid response in children with asthma: a literature review vol.45, pp.6, 2013, https://doi.org/10.1177/0300060516683877
  4. Pharmacogenetics of asthma: toward precision medicine vol.23, pp.1, 2013, https://doi.org/10.1097/mcp.0000000000000335
  5. Genetic variation in the glucocorticoid pathway involved in interindividual differences in the glucocorticoid treatment vol.18, pp.3, 2013, https://doi.org/10.2217/pgs-2016-0151
  6. PTGDR gene expression and response to dexamethasone treatment in an in vitro model vol.12, pp.10, 2013, https://doi.org/10.1371/journal.pone.0186957
  7. Pharmacogenetic and pharmacogenomic considerations of asthma treatment vol.13, pp.11, 2013, https://doi.org/10.1080/17425255.2017.1391215
  8. Identification of differentially expressed genes associated with asthma in children based on the bioanalysis of the regulatory network vol.18, pp.2, 2013, https://doi.org/10.3892/mmr.2018.9205
  9. Overview and challenges of current genetic research on allergic diseases in Korean children vol.6, pp.suppl1, 2013, https://doi.org/10.4168/aard.2018.6.s1.s77
  10. Targeting HDAC Complexes in Asthma and COPD vol.3, pp.3, 2013, https://doi.org/10.3390/epigenomes3030019