الفهرس 
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Abstract
he hereditary component of asthma is determined
polygenetically. The environmental component is implied
significantly by neuroimmune reactions occurring at the molecular
level. It should be emphasized that bronchial asthma is a disorder
whose primary cause can probably be traced in the disturbed
immunoregulatory mechanisms at the lymphocyte level, with
secondary overproduction of IgE class antibodies and allergic
inflammatory condition.
Glucocorticosteroid resistance is a complex problem. It may
be constitutional in character, or develop as a sequel to an
inflammatory process. It should be emphasized that each tissue
represents different sensitivity to GCs.
Polymorphisms present within the h-GR/NR3C1 gene may
inhibit formation of GR/GCS complexes reduce transcription and
cause transrepression of the genes encoding proteins synthesized
within framework of cellular response to GCs.
The aim of this study is to determine the correlation between
Bcl I single nucleotide polymorphism of h-GR/NR3C1 gene
promoter and resistance to glucocorticoid therapy with
development of severe form/difficult to treat bronchial asthma.
This study was conducted on a total of 60 age and sex
matched subjects. They were divided into 2 groups: Group I
(Severe asthmatic patients group) [n=40] including subjects with
severe bronchial asthma, Group I was further subdivided according to GINA classification into 2 subgroups: subgroup Ιa (severe
sensitive asthmatic patients, n=20), subgroup Ιb (severe resistant
asthmatic patients, n=20). Group II (control group) [n=20]
including healthy respiratory-free subjects. BclI single nucleotide
polymorphism of the human glucocorticoid receptor gene h-
GR/NR3C1 promoter was done by PCR-RFLP to all Subjects.
This study revealed a significantly greater bronchodilator
response in severe sensitive asthmatic patients after a one week
course of oral prednisone treatment, while steroid resistant group
showed no response in steroid resistant asthmatics. This indicates
that the degree of bronchodilator reversibility is impaired in severe
resistant asthmatic patients, as compared to, severe sensitive
asthmatic patients.
This study also revealed that allele G is particularly
associated with sensitivity to glucocorticoids. It increases the
cellular response to GCs. This explains the higher frequency of G
allele in severe sensitive asthmatic patients and the high frequency
of C allele in severe resistant asthmatic patients in the present
study.
The present study illustrated the role of BCL1
polymorphism of h-GR/NR3C1 gene in the pathogenesis of
bronchial asthma and development of glucocorticoids resistance;
where GG genotype was more frequent in asthmatic patients which
may aid in earlier diagnosis and management, While C allele was
more frequent in severe resistant asthmatic patients.