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01 October 2010

Frequencies of Bcl I, E22E, and N363S of h-GR/NR3C1 restriction fragment length polymorphisms of glucocorticoid receptor gene in Polish adult population

Tadeusz PietrasABCDEF, Michal PanekABCDEF, Izabela Kuprys-LipinskaB, Katarzyna OszajcaBCD, Radoslaw WujcikB, Piotr KunaD, Pawel GorskiD, Janusz SzemrajADFG

Med Sci Monit 2010; 16(10): CR475-479 :: ID: 881197

Abstract

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.

Keywords: Polymorphism, Genetic, Poland, Genotype, Polymorphism, Restriction Fragment Length - genetics, Genetics, Population, Gene Frequency, Base Sequence, Drug Resistance - drug effects, Receptors, Glucocorticoid - genetics

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