Association of <i>SLC22A1</i>, <i>SLC22A2</i>, <i>SLC47A1</i>, and <i>SLC47A2</i> Polymorphisms with Metformin Efficacy in Type 2 Diabetic Patients
Response to metformin, first-line therapy for type 2 diabetes mellitus (T2DM), exists interindividual variation. Considering that transporters belonging to the solute carrier (SLC) superfamily are determinants of metformin pharmacokinetics, we evaluated the effects of promoter variants in organic ca...
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MDPI AG
2022-10-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/10/2546 |
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| author | Peixian Chen Yumin Cao Shenren Chen Zhike Liu Shiyi Chen Yali Guo |
| author_facet | Peixian Chen Yumin Cao Shenren Chen Zhike Liu Shiyi Chen Yali Guo |
| author_sort | Peixian Chen |
| collection | DOAJ |
| description | Response to metformin, first-line therapy for type 2 diabetes mellitus (T2DM), exists interindividual variation. Considering that transporters belonging to the solute carrier (SLC) superfamily are determinants of metformin pharmacokinetics, we evaluated the effects of promoter variants in organic cation transporter 1 (OCT1) (<i>SLC22A1</i> rs628031), OCT2 (<i>SLC22A</i><i>2</i> rs316019), multidrug and toxin extrusion protein 1 (MATE1) (<i>SLC47A</i><i>1</i> rs2289669), and MATE2 (<i>SLC47A</i><i>2</i> rs12943590) on the variation in metformin response. The glucose-lowering effects and improvement of insulin resistance of metformin were assessed in newly diagnosed, treatment-naive type 2 diabetic patients of Han nationality in Chaoshan China (<i>n</i> = 93) receiving metformin. Fasting plasma glucose (FPG), fasting insulin (FINS), glycated hemoglobin A1 (HbA1<sub>C</sub>), homeostasis model assessment-insulin sensitivity (HOMA-IS), and homeostasis model assessment-insulin resistance (HOMA-IR) were the main metformin efficacy measurements. There were significant correlations between both <i>SLC47A1</i> rs2289669 and <i>SLC47A2</i> rs12943590 and the efficacy of metformin in individuals with T2DM. In normal weight T2DM patients, significant associations between the AA and GG genotypes of the rs2289669 variant of <i>SLC</i><i>47A1</i> and a greater reduction in FINS and HOMA-IR were detected. A significant correlation was observed between the AG genotype of the rs12943590 polymorphism of <i>SLC47A2</i> and a greater reduction in HOMA-IR. Gene–environment interaction analysis showed that in the FINS interaction model, the second-order of dose30_g-<i>SLC47A2</i> rs12943590 was statistically significant. The variants of <i>SLC47A1</i> rs2289669 and <i>SLC47A2</i> rs12943590 could be predictors of insulin resistance in type 2 diabetic patients treated with metformin. The second-order interaction of dose30_g-<i>SLC47A2</i> rs12943590 may have a significant effect on FINS in patients with T2DM on metformin treatment. These findings suggest that promoter variants of <i>SLC47A1</i> and <i>SLC47A2</i> are important determinants of metformin transport and response in type 2 diabetes mellitus. |
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| spelling | doaj.art-10bb95649af0439eab6a5801291d6fb72023-11-23T23:04:51ZengMDPI AGBiomedicines2227-90592022-10-011010254610.3390/biomedicines10102546Association of <i>SLC22A1</i>, <i>SLC22A2</i>, <i>SLC47A1</i>, and <i>SLC47A2</i> Polymorphisms with Metformin Efficacy in Type 2 Diabetic PatientsPeixian Chen0Yumin Cao1Shenren Chen2Zhike Liu3Shiyi Chen4Yali Guo5Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, ChinaDepartment of Endocrinology and Metabolism, the Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, ChinaDepartment of Endocrinology and Metabolism, the Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Endocrinology and Metabolism, the Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, ChinaDepartment of Endocrinology and Metabolism, the Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, ChinaResponse to metformin, first-line therapy for type 2 diabetes mellitus (T2DM), exists interindividual variation. Considering that transporters belonging to the solute carrier (SLC) superfamily are determinants of metformin pharmacokinetics, we evaluated the effects of promoter variants in organic cation transporter 1 (OCT1) (<i>SLC22A1</i> rs628031), OCT2 (<i>SLC22A</i><i>2</i> rs316019), multidrug and toxin extrusion protein 1 (MATE1) (<i>SLC47A</i><i>1</i> rs2289669), and MATE2 (<i>SLC47A</i><i>2</i> rs12943590) on the variation in metformin response. The glucose-lowering effects and improvement of insulin resistance of metformin were assessed in newly diagnosed, treatment-naive type 2 diabetic patients of Han nationality in Chaoshan China (<i>n</i> = 93) receiving metformin. Fasting plasma glucose (FPG), fasting insulin (FINS), glycated hemoglobin A1 (HbA1<sub>C</sub>), homeostasis model assessment-insulin sensitivity (HOMA-IS), and homeostasis model assessment-insulin resistance (HOMA-IR) were the main metformin efficacy measurements. There were significant correlations between both <i>SLC47A1</i> rs2289669 and <i>SLC47A2</i> rs12943590 and the efficacy of metformin in individuals with T2DM. In normal weight T2DM patients, significant associations between the AA and GG genotypes of the rs2289669 variant of <i>SLC</i><i>47A1</i> and a greater reduction in FINS and HOMA-IR were detected. A significant correlation was observed between the AG genotype of the rs12943590 polymorphism of <i>SLC47A2</i> and a greater reduction in HOMA-IR. Gene–environment interaction analysis showed that in the FINS interaction model, the second-order of dose30_g-<i>SLC47A2</i> rs12943590 was statistically significant. The variants of <i>SLC47A1</i> rs2289669 and <i>SLC47A2</i> rs12943590 could be predictors of insulin resistance in type 2 diabetic patients treated with metformin. The second-order interaction of dose30_g-<i>SLC47A2</i> rs12943590 may have a significant effect on FINS in patients with T2DM on metformin treatment. These findings suggest that promoter variants of <i>SLC47A1</i> and <i>SLC47A2</i> are important determinants of metformin transport and response in type 2 diabetes mellitus.https://www.mdpi.com/2227-9059/10/10/2546metforminsingle-nucleotide polymorphismpharmacogeneticstype 2 diabetes mellitus |
| spellingShingle | Peixian Chen Yumin Cao Shenren Chen Zhike Liu Shiyi Chen Yali Guo Association of <i>SLC22A1</i>, <i>SLC22A2</i>, <i>SLC47A1</i>, and <i>SLC47A2</i> Polymorphisms with Metformin Efficacy in Type 2 Diabetic Patients Biomedicines metformin single-nucleotide polymorphism pharmacogenetics type 2 diabetes mellitus |
| title | Association of <i>SLC22A1</i>, <i>SLC22A2</i>, <i>SLC47A1</i>, and <i>SLC47A2</i> Polymorphisms with Metformin Efficacy in Type 2 Diabetic Patients |
| title_full | Association of <i>SLC22A1</i>, <i>SLC22A2</i>, <i>SLC47A1</i>, and <i>SLC47A2</i> Polymorphisms with Metformin Efficacy in Type 2 Diabetic Patients |
| title_fullStr | Association of <i>SLC22A1</i>, <i>SLC22A2</i>, <i>SLC47A1</i>, and <i>SLC47A2</i> Polymorphisms with Metformin Efficacy in Type 2 Diabetic Patients |
| title_full_unstemmed | Association of <i>SLC22A1</i>, <i>SLC22A2</i>, <i>SLC47A1</i>, and <i>SLC47A2</i> Polymorphisms with Metformin Efficacy in Type 2 Diabetic Patients |
| title_short | Association of <i>SLC22A1</i>, <i>SLC22A2</i>, <i>SLC47A1</i>, and <i>SLC47A2</i> Polymorphisms with Metformin Efficacy in Type 2 Diabetic Patients |
| title_sort | association of i slc22a1 i i slc22a2 i i slc47a1 i and i slc47a2 i polymorphisms with metformin efficacy in type 2 diabetic patients |
| topic | metformin single-nucleotide polymorphism pharmacogenetics type 2 diabetes mellitus |
| url | https://www.mdpi.com/2227-9059/10/10/2546 |
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