Reza Moazzami, Mohammad Yahya Vahidi Mehrjardi, Ali Miri
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引用次数: 0
Abstract
Introduction: : Metformin, an oral hypoglycemic agent, is generally used as the first-line treatment in type 2 diabetes mellitus (T2DM) patients. The response to metformin varies between patients, and its mechanisms remain incompletely understood. Genetic variations in proteins involved in the pharmacodynamics and pharmacokinetics of metformin, like OCT1 transporter, are suspected to explain this difference. This study investigated the association of the response to metformin in T2DM patients with the presence of rs12208357 (R61C) variant in the SLC22A1 gene.
Materials and methods: We selected 100 patients who responded and 100 patients who did not respond to metformin monotherapy after 20 weeks according to their HbA1c level change. We investigated the effect of rs12208357 on the structure, function, and stability of OCT1 protein and its interaction with metformin by in silico tools. To determine the genotype of rs12208357 we used the ARMS-PCR technique.
Results: The in silico study indicated that rs12208357 probably changes OCT1 stability, function, interaction site, and binding energy to metformin in the extracellular domain. ARMS-PCR also showed the frequency of T and C alleles were significantly different between responders and non-responders (P-value = 0.014), also there is a significant difference in CC and CT/TT genotype frequency between responders and non-responders (P-value = 0.023).
Conclusion: Based on the in silico study and ARMS-PCR experiment results, the CC genotype has a better response to metformin therapy and the carrier of the T allele (CT and TT genotype) probably has complications in glycemic control by metformin.
期刊介绍:
Journal of Diabetes & Metabolic Disorders is a peer reviewed journal which publishes original clinical and translational articles and reviews in the field of endocrinology and provides a forum of debate of the highest quality on these issues. Topics of interest include, but are not limited to, diabetes, lipid disorders, metabolic disorders, osteoporosis, interdisciplinary practices in endocrinology, cardiovascular and metabolic risk, aging research, obesity, traditional medicine, pychosomatic research, behavioral medicine, ethics and evidence-based practices.As of Jan 2018 the journal is published by Springer as a hybrid journal with no article processing charges. All articles published before 2018 are available free of charge on springerlink.Unofficial 2017 2-year Impact Factor: 1.816.