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Genetic and Phenotypic Factors Affecting Glycemic Response to Metformin Therapy in Patients with Type 2 Diabetes Mellitusстатья
- Авторы: Vasileva Tatiana V., Komandresova Tatiana M., Nasykhova Yulia A., Barbitoff Yury A., Tonyan Ziravard N., Danilova Maria M., Nevzorov Ivan A., Mikhailova Anastasiia, Glavnova Olga, Yarmolinskaya Maria I., Sluchanko Evgenia I., Glotov Andrey S.
- Журнал: Genes
- Том: 13
- Номер: 1310
- Год издания: 2022
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Аннотация: Metformin is an oral hypoglycemic agent widely used in clinical practice for treatment ofpatients with type 2 diabetes mellitus (T2DM). The wide interindividual variability of response tometformin therapy was shown, and recently the impact of several genetic variants was reported. To assess the independent and combined effect of the genetic polymorphism on glycemic response tometformin, we performed an association analysis of the variants in ATM, SLC22A1, SLC47A1, andSLC2A2 genes with metformin response in 299 patients with T2DM. Likewise, the distribution ofallele and genotype frequencies of the studied gene variants was analyzed in an extended groupof patients with T2DM (n = 464) and a population group (n = 129). According to our results, onevariant, rs12208357 in the SLC22A1 gene, had a significant impact on response to metformin inT2DM patients. Carriers of TT genotype and T allele had a lower response to metformin comparedto carriers of CC/CT genotypes and C allele (p-value = 0.0246, p-value = 0.0059, respectively). To identify the parameters that had the greatest importance for the prediction of the therapy response to metformin, we next built a set of machine learning models, based on the various combinations of genetic and phenotypic characteristics. The model based on a set of four parameters, including gender, rs12208357 genotype, familial T2DM background, and waist–hip ratio (WHR) showed the highest prediction accuracy for the response to metformin therapy in patients with T2DM (AUC = 0.62 in cross-validation). Further pharmacogenetic studies may aid in the discovery of the fundamental mechanisms of type 2 diabetes, the identification of new drug targets, and finally, it could advance the development of personalized treatment.
- Добавил в систему: Васильева Татьяна Владимировна
Прикрепленные файлы
| № | Имя | Описание | Имя файла | Размер | Добавлен |
|---|---|---|---|---|---|
| 1. | genes-13-01310_statya_Scopus_Q2.pdf | genes-13-01310_statya_Scopus_Q2.pdf | 608,2 КБ | 1 февраля 2023 [VasilevaTV] |