Association of SLC22A1, SLC22A2, SLC47A1, and SLC47A2 Polymorphisms with Metformin Efficacy in Type 2 Diabetic Patients

Peixian Chen; Yumin Cao; Shenren Chen; Zhike Liu; Shiyi Chen; Yali Guo

doi:10.3390/biomedicines10102546

Biomedicines (Oct 2022)

Association of SLC22A1, SLC22A2, SLC47A1, and SLC47A2 Polymorphisms with Metformin Efficacy in Type 2 Diabetic Patients

Peixian Chen,
Yumin Cao,
Shenren Chen,
Zhike Liu,
Shiyi Chen,
Yali Guo

Affiliations

Peixian Chen: Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, China
Yumin Cao: Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, China
Shenren Chen: Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, China
Zhike Liu: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, China
Shiyi Chen: Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, China
Yali Guo: Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Shantou University Medical College, Shantou 515000, China

DOI: https://doi.org/10.3390/biomedicines10102546
Journal volume & issue: Vol. 10, no. 10
p. 2546

Abstract

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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) (SLC22A1 rs628031), OCT2 (SLC22A2 rs316019), multidrug and toxin extrusion protein 1 (MATE1) (SLC47A1 rs2289669), and MATE2 (SLC47A2 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 (n = 93) receiving metformin. Fasting plasma glucose (FPG), fasting insulin (FINS), glycated hemoglobin A1 (HbA1C), 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 SLC47A1 rs2289669 and SLC47A2 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 SLC47A1 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 SLC47A2 and a greater reduction in HOMA-IR. Gene–environment interaction analysis showed that in the FINS interaction model, the second-order of dose30_g-SLC47A2 rs12943590 was statistically significant. The variants of SLC47A1 rs2289669 and SLC47A2 rs12943590 could be predictors of insulin resistance in type 2 diabetic patients treated with metformin. The second-order interaction of dose30_g-SLC47A2 rs12943590 may have a significant effect on FINS in patients with T2DM on metformin treatment. These findings suggest that promoter variants of SLC47A1 and SLC47A2 are important determinants of metformin transport and response in type 2 diabetes mellitus.

Published in Biomedicines

ISSN: 2227-9059 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/biomedicines

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