The College of Pharmacy discussed the PhD dissertation entitle “The Association between the Genetic Polymorphism of GLP1R & DPP4 Genes with Serum GLP-1 Level and Response to Sitagliptin-Metformin Therapy in Iraqi T2DM Patient” by the student zainab Ahmad Attiya and her supervisor, Professor Dr. Shatha Hussain Ali in the clinical pharmacy Department.
The study aimed to evaluate the relationship of the rs3765467 polymorphism of the GLP1R gene and the rs6741949 polymorphism of the DPP4 gene with serum GLP-1 level and therapeutic response for sitagliptin -metformin treatment in T2DM individuals.
The study included a cross-sectional study involves selected patients with T2DM from those attending The Diabetes and Endocrinology Unit/ Baghdad Teaching Hospital – Medical City. The study enrolled 90 patients with T2DM (35 male; 55 female) who would be distributed according to their responses into two groups including (45 patients) who responded clinically and (45 patients) who failed to respond to the treatment. The response was assessed based on HbA1c level after 3 months of treatment, but not more than 12 month of continuous treatment with sitagliptin -metformin. A blood sample was collected from each patient after an overnight fast for at least eight hours. A portion of the blood sample was collected without EDTA to obtain serum. A part of serum used for the biochemical .The remaining serum was stored at -80°C until the assay of serum insulin and GLP-1 levels which were measured by ELISA. The samples collected in EDTA tubes were used for HbA1c measurement and DNA extraction, which was performed to analyze the target genes. DNA sequencing using Sanger’s technique was carried out to detect the SNP rs3765467 within the amplified region of the GLP1R promoter, while the SNP rs6741949 in the intronic region of the DPP4 gene was identified using HRM analysis.
In the case of the SNP (rs3765467) of GLP1R, it was not detected in a present study population of 90 Iraqi individuals. However, Sanger sequencing identified three nearby SNPs (rs3765466, rs910163 and rs910162). These SNPs showed no significant association with treatment response but were significantly associated with serum GLP-1 levels. While, the DPP4 SNP rs6741949 showed no effect on treatment response or GLP-1 level but it was associated with higher serum insulin and cholesterol levels.
The study recommended a future study with a large sample size and multicenter study is necessary, with a suitable follow-up period to better assess long-term outcomes. Additionally, it is recommended to consider patients’ genetic profiles when prescribing medications to optimize drug efficacy and minimize adverse effects.
