Thesis (M.Sc.) -Cairo University, 2023.

Bibliography: pages 76-90.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune disorder
characterized by decreased platelet count. While corticosteroids are a useful first-
line therapy for ITP patients, their long-term effectiveness is limited, and the
determinants of corticosteroid sensitivity in ITP patients remain largely unknown.
Silent information regulator 1 (SIRT1) is a histone deacetylase of nicotinamide
adenine dinucleotide (NAD+), which mainly exists in the nucleus, and is a member
of a family of well-studied mammalian sirtuins. SIRT1 interacts with protein
substrates in a variety of signaling pathways (such as Wnt and Notch), participates
in the regulation of most of the body’s physiological functions, and plays a central
regulatory role in cell proliferation, differentiation, senescence, apoptosis, and
metabolism.it is also related to the anti-inflammatory effect of corticosteroids.
Aim of the Work: The present work was done to study the prevalence and role of
SIRT1 SNP rs12778366 in ITP susceptibility and corticosteroids sensitivity.
Participants and Methods: Sixty patients with ITP as well as 60 age and sex-
matched normal healthy controls were included. SIRT1 rs12778366 SNP was
determined by allelic discrimination Taqman real-time PCR.
Results: Our study revealed that SIRT1 rs12778366 variants among ITP patients
were found to be the wild type T/T (81.7%), the heterozygous T/C (16.7%) and the
homozygous C/C genotype (1.7%), while among the control group were the wild
type T/T (90%), the heterozygous T/C (10%) and non were in the homozygous C/C
with no statistically significant difference between the 2 groups (p ˃0.05) and that
SIRT1 rs12778366 variants had no role as a risk factor of ITP susceptibility.
Regarding sensitivity to corticosteroids, patients who were sensitive to steroids
were found to be the wild type T/T (90%), the heterozygous T/C (10%) and non
were in the homozygous C/C, while ITP patients who were resistant to
corticosteroids, the wild type T/T (73.3%), the heterozygous T/C (23.3%) and the
homozygous C/C (3.3%) with no significant difference between the 2 groups (p
˃0.05) and that SIRT1 rs12778366 variants had no impact on prognosis or
treatment outcome.
Conclusion: SIRT1 rs12778366 had no role in ITP susceptibility, disease severity
or corticosteroid sensitivity.

Issued also as CD

Text in English and abstract in Arabic & English.