Study of the association between SIRT1 single nucleotide gene variant and corticosteroid response in Egyptian pediatric patients with primary immune thrombocytopenia /
فى الاطفال SIRT 1 دراسة ارتباط تعدد الجينى لجين المصرين المصابين بمرض نقص الصفائح الدموية المناعى ومدي الاستجابه للعلاج بالكورتيزون /
By Omnia Attia Saad; Supervised By Prof. Dr. Nevine Mohamed Bahaa Eldin Fouad, Asst. Prof. Marwa Abd Elhady Abd Elsamad, Dr. Doaa Salah Mahmoud
- 93 pages : illustrations ; 25 cm. + CD.
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.