الفهرس 
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Abstract
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with inflammatory syndrome that affects mainly women in child bearing age. It is caused by genetic, epigenetic, environmental and immune regulatory causes and affects many organs such as skin, joints, nervous and vascular systems, or kidneys with remissions and exacerbations giving the disease its clinical variability(Gordon et al., 2018). The hallmark for diagnosis is the presence of specific autoantibodies to self-antigens mainly nuclear antigen (double-stranded DNA (dsDNA), Smith antigen and ribonucleoproteins (Sm/RNP), anti-Sjögren’s-syndrome-related antigen A and B (SSA/Ro, and SSB/La, respectively), these antibodies are used in diagnosis and has a prognostic value as well (Dema & charles, 2016). Mycophenolate mofetil (MMF) is the prodrug which becomes activated when converted to mycophenolic acid (MPA). The MPA exerts its effect by inhibition the action of inosine-5’- monophosphatedehydrogenase (IMPDH) enzyme, it is the rate limiting enzyme in synthesis of gunosine nucleotide inside T and B lymphocytes. The MPA implies its effect on IMPDH making strong cytostatic effect on lymphocytes so suppressing the cell mediated and humoral immune response (Dall’Era, 2011). The Aim of this study: The aim of work is to examine the distribution of the T-275A and C-2152T single nucleotide polymorphisms (SNPs) in the UGT1A9 promoter region in patients with SLE as well as how these SNPs affected the pharmacokinetics of mycophenolic acid (MPA). Materials and methods: This study was conducted on 150 individual subdivided into two groups. The patient group included 50 systemic lupus patients selected from outpatient Clinics of Rheumatology and immunology department, Mansoura university hospitals. The control group included 100 apparently healthy subjects: 14 males & 86 females, They had no clinical evidence or family history of systemic lupus or other autoimmune diseases. 5mL venous blood was withdrawn from each subject for DNA extraction and MPA assay. Screening lab tests (CBC,C3,C4,ANA,Anti ds-DNA, creatinine, urine protein) were obtained from patients medical records. UGT1A9 c.-2152 C>T and c.-275 T>A polymorphism detection by (PCR-RFLP). The quantitative measurement of Mycophenolic Acid (MPA) in human serum is carried out by Dimension® X pand plus clinical chemistry system. Results: •Increase of anemia frequency in patients with c.-2152 C>T mutation. •Increase of frequency of GIT complications in patients with c.-275 T>A mutation. •Frequency of leucopenia is observed with increased MPA level. •UGT1A9 polymorphism in promoter region c.-275T>A (TA+AA) and c.-2152C>T (CT) are associated with increase hepatic glucurination of mycophenolic acid and low trough level of the drug in systemic lupus patients. Recommendations: It is recommended to carry out genotyping for UGT 1A9 polymorphism c.-275T>A and c.-2152 C>T before starting mycophenolic acid immunosuppressive drug to determine the suitable dose for each patients and avoid side effects of the drug.