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.
Dyslipidemia is the main risk factor for coronary artery disease and is characterized by alterations in concentrations of lipids, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triacylglycerols. The participation of several genes in the development of dyslipidemia has been evidenced. Genetic variants in SLC22A1 have been associated with elevated cholesterol and LDL-c levels. The aim of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) in the SLC22A1 gene with atherogenic risk lipid levels in Mexican women. Anthropometric and biochemical measurements were performed, and four SNPs in SLC22A1 were genotyped by real-time polymerase chain reaction. The Hardy-Weinberg equilibrium was verified, and haplotype frequencies were calculated. We found significant differences between the allele frequencies of the SNPs analyzed with those reported in Mexico and in the world, which could be due to differences in the historical admixture of the women studied. Generalized linear models were evaluated to determine the association between genotypes and haplotypes with lipids levels. We identified a significant increase in total cholesterol and LDL-c levels in women who were carriers of the GA and AG genotypes of the polymorphisms rs628031 and rs594709, respectively, significant effect that is also shown in a dominant inheritance model. Interestingly, we identified an important relationship of the AGC-GAT haplotype with the elevation in LDL-c levels and AGA-GAT haplotype with the elevation in HDL-c levels. On the other hand, we found a strong linkage disequilibrium between the polymorphisms studied. Our results show that variants in the SLC22A1 gene influence serum levels of atherogenic risk lipids, suggesting that these variants probably affect the function of organic cation transporter-1 and therefore, on the regulation of lipid metabolism.
The metabolic syndrome (MS) is a set of metabolic abnormalities increasing the risk of developing diabetes and caridaca coronary disease. The SLC22A1 gene among different population groups, related to carnitine metabolism and acylcarnitine plasma levels associated with metabolic diseases. Objective: To evaluate the rs rs628031 variant in the SLC22A1 gene and its relationship with the metabolic syndrome in women from the state of Guerrero. Methodology: A cross-sectional study was conducted in 438 patients. Anthropometric and biochemical measurements were made. The rapid nonenzymatic technique was used for DNA extraction from leukocytes isolated from peripheral blood for genotyping PCR, using TaqMan probes. Results: a relationship between rs628031 polymorphism and serum total cholesterol proteins was identified in the carriers of the A / A variant with respect to the carriers of the G / G and G / A variant (p 0.0015), in addition to LDL-cholesterole. in carriers of the A / A variant compared to the other genotypes (p = 0.0007).
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