Metformin is a widely used and effective agent in type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome (PCOS). Yet, the mechanisms of action and the occurrence of side effects (e.g. abdominal bloating and pain), are still poorly understood. Since organic cation transporters (OCTs) are responsible for the hepatic and renal transport of metformin, we investigated a series of short nucleotide polymorphisms (SNPs) in the OCT genes in PCOS and in T2DM patient samples from either our PCOS patient registry or the Graz Diabetes Registry for Biomarker Research (GIRO).
After DNA isolation from plasma in 181 PCOS samples and 44 T2DM samples followed by a subsequent polymerase chain reaction (PCR) with a combined TaqMan assay, we compared 17 SNPs (rs456598, rs461473, rs3798174, rs7766568, rs316007, rs3798167, rs662301, rs2048327, rs376563, rs622591, rs9295125, rs3798172, rs2197296, rs12208357, rs34059508, rs628031 and rs3777392) from OCT1 and OCT3 transporters.
Data of the study participants were analyzed according to the presence or absence of documented metformin-induced side effects. The distributions of different genotypes of the rs2197296 locus in the SLC22A1 gene, the rs376563 locus in the SLC22A2 gene and the rs3798167 locus in the SLC22A3 gene were statistically significant between the two groups. The effect was shown by a higher minor allele frequency in the group with documented metformin associated side effects (χ(2) = 3.953, P = 0.047, χ(2) = 7.342, P = 0.025 and χ(2) = 12.251, P = 0.002 respectively).
In conclusion, we found three specific allelic variants in OCT candidate genes with distinct associations for side effects in metformin users either in PCOS or in T2DM. Therefore, those variants can be further investigated to better understand the metformin-associated side effects.
22 May 2021 - 26 May 2021