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. 2019 Oct;59(10):1384-1390.
doi: 10.1002/jcph.1425. Epub 2019 Apr 23.

Altered Glycemic Control Associated With Polymorphisms in the SLC22A1 (OCT1) Gene in a Mexican Population With Type 2 Diabetes Mellitus Treated With Metformin: A Cohort Study

Carlos Alberto Reséndiz-Abarca  1   2 , Eugenia Flores-Alfaro  1 , Fernando Suárez-Sánchez  2 , Miguel Cruz  2 , Adán Valladares-Salgado  2 , Luz Del Carmen Alarcón-Romero  1 , Miguel Alexander Vázquez-Moreno  2 , Niels Agustín Wacher-Rodarte  3 , Jaime Héctor Gómez-Zamudio  2
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Altered Glycemic Control Associated With Polymorphisms in the SLC22A1 (OCT1) Gene in a Mexican Population With Type 2 Diabetes Mellitus Treated With Metformin: A Cohort Study

Carlos Alberto Reséndiz-Abarca et al. J Clin Pharmacol. 2019 Oct.

Abstract

The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells. The aim of this study was to evaluate whether genetic variations in the SLC22A1, SLC22A2, and SLC47A1 genes could be associated with an altered response to metformin in patients with type 2 diabetes mellitus. A cohort study was conducted in 308 individuals with a diagnosis of type 2 diabetes mellitus of less than 3 years and who had metformin monotherapy. Three measurements of blood glycated hemoglobin (HbA1c ) were obtained at the beginning of the study and after 6 and 12 months. Five polymorphisms were analyzed in the SLC22A1 (rs622342, rs628031, rs594709), SLC22A2 (rs316019), and SLC47A1 (rs2289669) genes by real-time polymerase chain reaction. The results showed a significant association among genotypes CC-rs622342 (β = 1.36; P < .001), AA-rs628031 (β = 0.98; P = .032), and GG-rs594709 (β = 1.21; P = .016) in the SLC22A1 gene with an increase in HbA1c levels during the follow-up period. Additionally, a significant association was found in the CGA and CAG haplotypes with an increase in HbA1c levels compared to the highest-frequency haplotype (AGA). In conclusion, the genetic variation in the SLC22A1 gene was significantly related to the variation of the HbA1c levels, an important indicator of glycemic control in diabetic patients. This information may contribute to identifying patients with an altered response to metformin before starting their therapy.

Keywords: SLC22A1; SLC22A2; SLC47A1; Type 2 diabetes mellitus; metformin.

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