CLINICAL IMMUNOLOGY
Influence of glucocorticoid receptor gene NR3C1 646 C>G polymorphism on glucocorticoid resistance in asthmatics: a preliminary study
Submission date: 2015-04-24
Final revision date: 2015-06-30
Acceptance date: 2015-07-01
Publication date: 2015-10-15
Cent Eur J Immunol 2015;40(3):325-330
KEYWORDS
asthmaglucocorticoid receptorglucocorticoid resistancerestriction fragment length polymorphismsingle nucleotide polymorphism
ABSTRACT
Background: Glucocorticoid receptor gene polymorphism (NR3C1 646 C>G) may play an important role in the development of severe bronchial asthma and resistance to glucocorticoids (GCs).
Objective: The aim of the present study was to determine the relation between the 646 C>G polymorphism of the glucocorticoid receptor gene (NR3C1) and resistance to GCs with development of severe bronchial asthma.
Material and methods: This case-control study included 40 patients with severe bronchial asthma and 20 apparently healthy controls. Atopic status was determined by skin prick test reaction to the most common locally-encountered allergens. GCs reversibility test was performed to differentiate between GCs sensitive and GCs resistant asthma. For all subjects, analysis of the glucocorticoid receptor gene polymorphism (NR3C1 646 C>G) was done using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).
Results: The frequencies of NR3C1 646 C>G genotypes and alleles differed significantly between asthmatic patients and controls. The frequencies of the CC genotype and C allele carriers were significantly higher among asthmatics than among controls, and also among GCs sensitive asthmatics than among GCs resistant asthmatics. However, NR3C1 646 C>G genotypes and alleles frequencies did not differ significantly according to the atopic status in asthmatics.
Conclusions: The too small sized of the investigated groups is a shortcoming of this study. Nevertheless, the observed variations demonstrate a marked association of NR3C1 646 C>G CC genotype with the development of bronchial asthma and a higher frequency of the C allele among GCs sensitive asthmatics. Large-scale studies are required to investigate the association between polymorphisms of the NR3C1 gene and GCs resistance among asthmatic patients.
Objective: The aim of the present study was to determine the relation between the 646 C>G polymorphism of the glucocorticoid receptor gene (NR3C1) and resistance to GCs with development of severe bronchial asthma.
Material and methods: This case-control study included 40 patients with severe bronchial asthma and 20 apparently healthy controls. Atopic status was determined by skin prick test reaction to the most common locally-encountered allergens. GCs reversibility test was performed to differentiate between GCs sensitive and GCs resistant asthma. For all subjects, analysis of the glucocorticoid receptor gene polymorphism (NR3C1 646 C>G) was done using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).
Results: The frequencies of NR3C1 646 C>G genotypes and alleles differed significantly between asthmatic patients and controls. The frequencies of the CC genotype and C allele carriers were significantly higher among asthmatics than among controls, and also among GCs sensitive asthmatics than among GCs resistant asthmatics. However, NR3C1 646 C>G genotypes and alleles frequencies did not differ significantly according to the atopic status in asthmatics.
Conclusions: The too small sized of the investigated groups is a shortcoming of this study. Nevertheless, the observed variations demonstrate a marked association of NR3C1 646 C>G CC genotype with the development of bronchial asthma and a higher frequency of the C allele among GCs sensitive asthmatics. Large-scale studies are required to investigate the association between polymorphisms of the NR3C1 gene and GCs resistance among asthmatic patients.
REFERENCES (24)
1.
Bousquet J, Mantzouranis E, Cruz AA, et al. (2010): Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organization Consultation on Severe Asthma. J Allergy Clin Immunol 126: 926-938.
2.
Pietras T, Panek M, Tworek D, et al. (2011):The Bcl I single nucleotide polymorphism of the human glucocorticoid receptor gene h-GR/NR3C1 promoter in patients with bronchial asthma: pilot study. Mol Biol Rep 38: 3953-3958.
3.
Kino T, De Martino M, Charmandari E, et al. (2003): Tissue glucocorticoid resistance/hypersensitivity syndromes. J Steroid Biochem Mol Biol 85: 457-467.
4.
Bamberger C, Bamberger A, de Castro M, et al. (1995): Glucocorticoid receptor beta, a potential endogenous inhibitor of glucocorticoid action in humans. J Clin Invest 95: 2435-2441.
5.
Ito K, Chung K, Adcock I (2006): Update on glucocorticoid action and resistance. J Allergy Clin Immunol 117: 522-543.
6.
Beato M, Chalepakis G, Schauer M, et al. (1989): DNA regulatory elements for steroid hormones. J Steroid Biochem Mol Biol 32: 737-747.
7.
Panek M, Pietras T, Kupryś-Lipińska I, et al. (2010): The analysis of the factors influencing the development of glucocorticoid resistance in the etiopathogenesis of severe bronchial asthma. Postepy Biochem 56: 373-382.
8.
Kmyta V, Prystupa L (2015): Influence of Bcl-1 gene polymorphism of glucocortucoid receptor on phenotypic expressions of bronchial asthma. Clin Transl Allergy 5: 10.
9.
Van Rossum E, Koper J, van den Beld A, et al. (2003): Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index. Clin Endocrinol 59: 585-592.
10.
Derijk R, de Kloet E (2008): Corticosteroid receptor polymorphisms: determinants of vulnerability and resilience. Eur J Pharmacol 583: 303-311.
11.
Nicolaides N, Galata Z, Kino T, et al. (2010): The human glucocorticoid receptor: molecular basis of biologic function. Steroids 75: 1-12.
12.
De Iudicibus S, Franca R, Martelossi S, et al. (2011): Molecular mechanism of glucocorticoid resistance in inflammatory bowel disease. World J Gastroenterol 17: 1095-1108.
13.
Rosmond R, Chagnon YC, Chagnon M, et al. (2000): A polymorphism of the 5’-flanking region of the glucocorticoid receptor gene locus is associated with basal cortisol secretion in men. Metabolism 49: 1197-1199.
14.
van Rossum EF, Koper JW, Huizenga NA, et al. (2002): A polymorphism in the glucocorticoid receptor gene, which decreases sensitivity to glucocorticoids in vivo, is associated with low insulin and cholesterol levels. Diabetes 51: 3128-3134.
15.
Koper JW, Stolk RP, de Lange P, et al. (1997): Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance. Hum Genet 99:663-668.
16.
Global Strategy for Asthma Management and Prevention (2009): Global Initiative for Asthma (GINA) NHLB. Available at http://www.ginasthma.org/acces... March 2015.
17.
Miller MR, Hankinson J, Brusasco V, et al. (2005): ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J 26: 319-338.
18.
Panek M, Pietras T, Fabijan A, et al. (2013): Effect of glucocorticoid receptor gene polymorphisms on asthma phenotypes. Exp Ther Med 5: 572-580.
19.
Charmandari E, Kino T, Ichijo T, et al. (2008): Generalized glucocorticoid resistance: clinical aspects, molecular mechanisms, and implications of a rare genetic disorder. J Clin Endocrinol Metab 93: 1563-1572.
20.
Maltese P, Canestrari E, Palma L, et al. (2009): High resolution melting (HRM) analysis for the detection of ER22/23EK, BclI, and N363S polymorphisms of the glucocorticoid receptor gene. J Steroid Biochem Mol Biol 113: 269-274.
21.
Kostik MM, Klyushina AA, Moskalenko MV, et al. (2011): Glucocorticoid receptor gene polymorphism and juvenile idiopathic arthritis. Pediatr Rheumatol Online J 9: 2.
22.
DeRijk RH, Schaaf M, de Kloet ER (2002): Glucocorticoid receptor variants: clinical implications. J Steroid Biochem Mol Biol 81: 103-122.
23.
Manenschijn L, van den Akker EL, Lamberts SW, et al. (2009): Rossum EF. Clinical features associated with glucocorticoid receptor polymorphisms. An overview. Ann N Y Acad Sci 1179: 179-198.
24.
Peden DB (2000): Development of atopy and asthma: candidate environmental influences and important periods of exposure. Environ Health Perspect 108: 475-482.
Share
RELATED ARTICLE
| eISSN: | 1644-4124 |
| ISSN: | 1426-3912 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
