The Faculty of Pharmacy discussed the PhD dissertation in Clinical Pharmacy entitled “Study of Association between Adhesion Molecule α4-Integrin Gene Polymorphism and Response to Natalizumab in a Sample of Iraqi Patients with Multiple Sclerosis” by Fadia Thamir Ahmed and her supervisors, Prof. Dr. Shatha Hussien Ali and Assist. Prof. Dr. Gheyath Abd Ali Shallal. The study aimed to assess the prevalence of the 3061 G/A (rs1143676) and 256 A/G,T (rs200000911) single nucleotide polymorphisms in the integrin α-4 subunit gene and their association with response to natalizumab in a sample of Iraqi patients with multiple sclerosis. This cross-sectional study was carried out in the Neurology Unit, Baghdad Teaching Hospital in Medical City/Baghdad, Iraq, under the supervision of a specialized neurologist from March 2022 until August 2023. Seventy patients of both genders who were already diagnosed with multiple sclerosis and had been receiving Natalizumab for at least 12 months were enrolled in the study. The sample was categorized into groups according to their response to natalizumab treatment (responders and non-responders). A polymerase chain reaction and Sanger’s sequencing of the extracted deoxyribonucleic acid were performed to identify the polymorphism in the integrin α-4 subunit gene promoter region. The 3061 AG genotype was significantly present (p-value 0.024) in the non-responders’ group and appeared to increase the propensity of being non-responders with a positive correlation (Phi-coefficient of 0.294). Additionally, there is a positive and significant likelihood of being a natalizumab non-responder (p-value: 0.026, OR: 3.433) when the patient has the AG variant as compared to the AA variant. For the 256 A/T polymorphism, the results revealed the existence of two additional intronic mutations (rs936587744 (T/C) and rs2305588 (T/C)). All three later genetic polymorphisms appeared to have a non-significant impact on the responsiveness to natalizumab (p-values of 0.898, 0.974, and 0.485, respectively).

 

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