The Effects of (rs3765467) polymorphism in the gene encoding GLPR1 on Serum GLP1 Level and Response to Sitagliptin in Combination with Metformin Therapy in Iraqi Type 2 Diabetics Patients

The dipepdityl peptidase-4 (DPP-4) inhibitors, which prevent incretin degradation, have become popular oral hypoglycemic agents for type 2 diabetes. Despite the wide use of DPP-4 inhibitors, little is known of clinical and pharmacogenomics factors that specifically associated with DPP-4 inhibitor treatment response. Meanwhile, a genetics studies identify important factors involved in the progression of diabetes disease, and identify individuals at risk of developing T2DM. Purpose of present study is to assess the possible association of (rs3765467) polymorphism in the gene encoding GLP1R with serum level of GLP1 and glycemic response for the treatment with sitagliptin in combination with metformin in Iraqi diabetic patients. The results indicated that SNP (rs3765467) was not detected in our study population of 90 individuals. However, Sanger sequencing had successfully identified three SNPs for the study population, including rs3765466, rs910163& (rs910162), located within the same region of the target SNP, rs3765467, in the gene encoding GLP1R. Furthermore, these SNPs (rs3765466), (rs910163) & (rs910162) show no significant effect on the response to the treatment based on HbAIc level (patients with HbA1c of less than or equal to 7.0% are classified as clinical responders, while those with HbA1c greater than 7.0% are classified as non-responders), but these SNPs significantly affect the serum GLP1 level. Additionally, (rs910163) & (rs910162) genotypes were significantly associated with serum creatinine levels, suggesting a potential role of the (rs910163) & (rs910162) variant in renal function regulation.