The effect of BclI polymorphism of NR3C1 gene on asthma phenotypes in Egyptian children

INTRODUCTION Bronchial asthma (BA) is a chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction and bronchospasm. It has increasing incidence and prevalence worldwide. Bronchial asthma is determined by many environmental and genetic factors, the clinical picture occurs as a result of complex interactions among genes, and the mutual influence of a genotype and environment upon each other. Glucocorticoids (GCs) constitute the basic group of medication used to control inflammatory condition in patient with bronchial asthma; they regulate expression of specific genes within the cell nuclei via the Glucocorticoids \ Glucocorticoid receptor complex (GC\GR). It has been estimated that approximately 100 genes are involved in the pathogenesis of asthma, NR3C1 gene (nuclear receptor subfamily 3, group C, member 1) is one of them, it encodes glucocorticoid receptor (GR) h-GR/NR3C1 which is localized on chromosome 5q31-q32 and consists of nine exons. The molecular mechanism of action of GCs involves binding of the specific ligand/glucocorticoid receptor to the sequences of regulator genes encoding the synthesis of antiinflammatory proteins determining the clinical effects of GCs. About 2571 polymorphisms of this gene are known, but the most common is the Bcl1 gene polymorphism of GR. BclI (rs41423247) is formed as a result of changes in a single base. A C/G single nucleotide polymorphism (SNP) within the h-GR/NR3C1 gene promoter has been localized in the intron 647 bp away from the exon/intron binding site. BclI polymorphism (C/G) within h-GR/NR3C1 gene promoter demonstrates correlations with sensitivity to steroids, and may play an important role in the development of BA and resistance to GCs in severe bronchial asthma. Original article