Laboratorio de Investigación en Epidemiología Clínica y Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México.
Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades "Bernardo Sepúlveda," Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.
J Clin Pharmacol. 2019 Oct;59(10):1384-1390. doi: 10.1002/jcph.1425. Epub 2019 Apr 23.
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 (HbA ) 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 HbA levels during the follow-up period. Additionally, a significant association was found in the CGA and CAG haplotypes with an increase in HbA 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 HbA 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.
有机阳离子转运蛋白 OCT1 和 OCT2 以及多药和毒素外排转运蛋白 MATE1 分别由 SLC22A1、SLC22A2 和 SLC47A1 基因编码，负责肠细胞、肝细胞和肾细胞中二甲双胍的吸收。本研究旨在评估 SLC22A1、SLC22A2 和 SLC47A1 基因的遗传变异是否与 2 型糖尿病患者对二甲双胍的反应改变有关。对 308 例诊断为 2 型糖尿病且病程少于 3 年且接受二甲双胍单药治疗的患者进行了队列研究。在研究开始时以及 6 个月和 12 个月后，对血液糖化血红蛋白（HbA ）进行了三次测量。通过实时聚合酶链反应分析了 SLC22A1（rs622342、rs628031、rs594709）、SLC22A2（rs316019）和 SLC47A1（rs2289669）基因中的五个多态性。结果显示，SLC22A1 基因中 CC-rs622342（β=1.36；P<.001）、AA-rs628031（β=0.98；P=.032）和 GG-rs594709（β=1.21；P=.016）基因型之间存在显著关联，HbA 水平在随访期间升高。此外，与最高频率单倍型（AGA）相比，CGA 和 CAG 单倍型与 HbA 水平升高之间存在显著关联。结论：SLC22A1 基因的遗传变异与 HbA 水平的变化显著相关，HbA 水平是糖尿病患者血糖控制的重要指标。这些信息可能有助于在开始治疗之前识别对二甲双胍反应改变的患者。
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