BACKGROUND: Polymorphism of the gene encoding the glucocorticoid receptor - h-GR/NR3C1 demonstrates close genetic and biochemical correlation with etiopathogenesis of metabolic, cardiovascular, hematologic, and mental disorders. The natural variability of DNA sequence within the h-GR gene affects both the conformation and the activity of glucocorticoid receptors. Modifications of the amino acid receptor structure give rise to disturbances of the receptor-hormone complex interaction with many genes responsible for normal cellular function. Transactivation, or transrepression, of the genes encoding proteins synthesized within the framework of cellular response to glucocorticosteroids is 1 among many molecular pathways leading to the development of resistance to anti-inflammatory drugs. MATERIAL/ METHODS: A group of 70 healthy participants, with no history of asthma or atopic conditions, qualified for the study. Genotyping was accomplished using PCR-RFLP method. RESULTS: In healthy, nonatopic population, within the h-GR gene promoter, a polymorphism of Bcl I: GG, GC, and CC occurring with 0.129/0.471/0.40 frequency, were identified. Two polymorphisms were identified in exon 2 at 1220 and 198 position in the h-GR gene: N363S (AA, AG occurring with 0.9/0.1 frequency) and ER22/23EK (GG, GC occurring with 0.843/0.157 frequency). CONCLUSIONS: The frequency of polymorphisms occurring within the h-GR gene has not been assessed to date in the Polish population. The present study is the first attempt of such estimation. The study is an introduction to more-detailed analysis of the correlation between the occurrence of h-GR gene polymorphisms, and the development of severe, steroid-resistant bronchial asthma.
BACKGROUND: Polymorphism of the gene encoding the glucocorticoid receptor - h-GR/NR3C1 demonstrates close genetic and biochemical correlation with etiopathogenesis of metabolic, cardiovascular, hematologic, and mental disorders. The natural variability of DNA sequence within the h-GR gene affects both the conformation and the activity of glucocorticoid receptors. Modifications of the amino acid receptor structure give rise to disturbances of the receptor-hormone complex interaction with many genes responsible for normal cellular function. Transactivation, or transrepression, of the genes encoding proteins synthesized within the framework of cellular response to glucocorticosteroids is 1 among many molecular pathways leading to the development of resistance to anti-inflammatory drugs. MATERIAL/ METHODS: A group of 70 healthy participants, with no history of asthma or atopic conditions, qualified for the study. Genotyping was accomplished using PCR-RFLP method. RESULTS: In healthy, nonatopic population, within the h-GR gene promoter, a polymorphism of Bcl I: GG, GC, and CC occurring with 0.129/0.471/0.40 frequency, were identified. Two polymorphisms were identified in exon 2 at 1220 and 198 position in the h-GR gene: N363S (AA, AG occurring with 0.9/0.1 frequency) and ER22/23EK (GG, GC occurring with 0.843/0.157 frequency). CONCLUSIONS: The frequency of polymorphisms occurring within the h-GR gene has not been assessed to date in the Polish population. The present study is the first attempt of such estimation. The study is an introduction to more-detailed analysis of the correlation between the occurrence of h-GR gene polymorphisms, and the development of severe, steroid-resistant bronchial asthma.
Authors: Michał Panek; Tadeusz Pietras; Artur Fabijan; Jan Zioło; Łukasz Wieteska; Beata Małachowska; Wojciech Fendler; Janusz Szemraj; Piotr Kuna Journal: Inflammation Date: 2015-08 Impact factor: 4.092
Authors: Michał Gabriel Panek; Michał Seweryn Karbownik; Karol Maksymilian Górski; Marcelina Koćwin; Grzegorz Kardas; Mateusz Marynowski; Piotr Kuna Journal: Clin Transl Allergy Date: 2022-07-02 Impact factor: 5.657