V klinickej praxi pozorujeme interindividuálne rozdiely v účinku metformínu u pacientov s diabetom mellitom 2. typu, na ktorých sa pravdepodobne podieľajú aj genetické faktory. Cieľom tejto štúdie bolo zistiť možný vzťah variantov génov kódujúcich transportné bielkoviny metformínu [organický katiónový transportér 1 (OCT1) (gén SLC22A1), multidrug and toxin extrusion 1(MATE1) (SLC47A1) a MATE2 (SLC47A2)] s odpoveďou na liečbu metformínom. Efekt 6-mesačnej monoterapie metformínom sme sledovali v skupine 148 pacientov s novodiagnostikovaným diabetom mellitom 2. typu, liečených pre diagnózu diabetu metformínom. Priemerný pokles hladiny glykovaného hemoglobínu (HbA1c) bol 0,66 ± 0,08 %. Genotypy SLC22A1 rs683369 C > G, SLC47A1 rs8065082 C > T a SLC47A2 rs12943590 G > A boli stanovené metódou PCR s následnou analýzou kriviek topenia. Spomedzi sledovaných variantov génov sme v multivariantnom lineárnom modeli dokázali signifikantne väčší pokles HbA1c pre minoritnú T-alelu SLC47A1 rs8065082 (β = 0,19, 95 % CI 0,02 – 0,35, p = 0,032). V multivariantnom logistickom modeli bola T-alela tiež signifikantne asociovaná s vyššou šancou dosiahnutia liečebného cieľa (HbA1c < 7 %): pomer šancí (OR) 1,87 (95 % CI 1,04 – 3,37, p = 0,038). Naše výsledky ukazujú, že prítomnosť každej T-alely v genotype SLC47A1 rs8065082 je spojená s poklesom glykovaného hemoglobínu o 0,19 % väčším po 6 mesiacoch monoterapie metformínom. Tieto výsledky by mohli v budúcnosti prispieť k personalizácii liečby diabetu mellitu 2. typu.

In clinical practice we observe important interindividual variability in glucose-lowering effect of metformin in type 2 diabetic patients with probable contribution of genetic factors. The aim of this study was to investigate the possible relationship of variants of genes encoding metformin transporter proteins including organic cation transporter 1 (OCT1) (gene SLC22A1), multidrug and toxin extrusion 1 (MATE1) (SLC47A1) and MATE2 (SLC47A2) with the response to metformin treatment. Effect of 6-month monotherapy with metformin were followed in a group of 148 drug-naive patients with newly diagnosed type 2 diabetes treated with metformin from the time of diagnosis of diabetes for at least 6 months. Mean decrease in glycated haemoglobin (HbA1c) was 0.66 ± 0.08 %. Genotypes for SLC22A1 rs683369 C > G, SLC47A1 rs8065082 C > T and SLC47A2 rs12943590 G > A were determined with PCR followed by melting curve analysis. Among the gene variations we observed in the multivariate linear model a significantly greater decrease in HbA1c for the minor T-allele of SLC47A1 rs8065082 (β = 0.19, 95 % CI 0.02 to 0.35, p = 0.032). In the multivariate logistic model T-allele was also significantly associated with a higher chance of achieving therapeutic goal (HbA1c < 7 %): odds ratio (OR) 1.87 (95 % CI 1.04 to 3.37, p = 0.038). Our results indicate that each T-allele in SLC47A1 rs8065082 genotype is associated with incremental, by 0.19 % higher reduction of glycated haemoglobin during 6-month metformin treatment. In the future these results could contribute to personalization of type 2 diabetes treatment.

Pharmacogenetic study of gene variants encoding metformin transporters in patients with diabetes mellitus type 2