RESUMEN
OBJECTIVE: Metformin is the most widely used oral antidiabetic drug for the treatment of type 2 diabetes (T2D). So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin. However, there is no information on the influence of genetic variations within these genes on the side effects of metformin. In this study, we assessed whether five single-nucleotide polymorphisms and two indel polymorphisms are associated with the side effects of metformin in patients with T2D. METHODS: Seven polymorphisms in OCT1, OCT2, and MATE1 genes were compared between 53 T2D patients with side effects of metformin and 193 metformin users without symptoms of metformin intolerance. RESULTS: We found a statistically significant association between the A allele of the rs628031 (P=0.012, odds ratio=0.389, confidence interval 95% [0.186-0.815]) as well as 8 bp insertion (rs36056065) in the OCT1 gene (P=0.002, odds ratio=0.405, confidence interval 95% [0.226-0.724]) and the presence of the side effects of metformin. CONCLUSION: Two genetic variations in OCT1 that are in strong linkage disequilibrium may predispose toward an increased prevalence of the side effects of metformin in patients with T2D.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Tracto Gastrointestinal/patología , Metformina/uso terapéutico , Proteínas de Transporte de Catión Orgánico/genética , Transportador 1 de Catión Orgánico/genética , Polimorfismo de Nucleótido Simple/genética , Índice de Masa Corporal , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/genética , Femenino , Estudios de Asociación Genética , Humanos , Hipoglucemiantes/uso terapéutico , Desequilibrio de Ligamiento/genética , Masculino , Metformina/efectos adversos , Persona de Mediana Edad , Transportador 2 de Cátion OrgánicoRESUMEN
Adenosine plays an important part in the cardiac response to ischemia and reperfusion. The human adenosine receptor A3 (A3R), along with other adenosine receptors, is involved in mediation of those effects. The aim of the study was to ascertain whether the nonsynonymous single-nucleotide polymorphism (SNP) I248L (reference SNP ID: rs35511654) located in the A3R gene is associated with coronary heart disease (CHD). DNA samples from 683 individuals with CHD and from 826 control subjects selected from the Latvian Genome Database were successfully screened for rs35511654 using the TaqMan SNP Genotyping Assay. We observed a significantly decreased frequency of the rs35511654 C allele in a group of CHD patients compared with that in controls (p = 0.009). The association remained significant after adjustment for age, sex, and other nongenetic factors (p = 0.02). These results suggest that A allele of rs35511654 may predispose to CHD.