Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Schweighofer, N; Strasser, M; Obermayer, A; Trummer, O; Sourij, H; Sourij, C; Obermayer-Pietsch, B.
Identification of Novel Intronic SNPs in Transporter Genes Associated with Metformin Side Effects.
Genes (Basel). 2023; 14(8): 1609 Doi: 10.3390/genes14081609 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Leading authors Med Uni Graz

Schweighofer Natascha

Trummer Olivia

Co-authors Med Uni Graz

Obermayer-Pietsch Barbara

Ramirez-Obermayer Anna Maria Antonia

Sourij Caren

Sourij Harald

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Abstract:

Metformin is a widely used and effective medication in type 2 diabetes (T2DM) as well as in polycystic ovary syndrome (PCOS). Single nucleotide polymorphisms (SNPs) contribute to the occurrence of metformin side effects. The aim of the present study was to identify intronic genetic variants modifying the occurrence of metformin side effects and to replicate them in individuals with T2DM and in women with PCOS. We performed Next Generation Sequencing (Illumina Next Seq) of 115 SNPs in a discovery cohort of 120 metformin users and conducted a systematic literature review. Selected SNPs were analysed in two independent cohorts of individuals with either T2DM or PCOS, using 5'-3'exonucleaseassay. A total of 14 SNPs in the organic cation transporters (OCTs) showed associations with side effects in an unadjusted binary logistic regression model, with eight SNPs remaining significantly associated after appropriate adjustment in the discovery cohort. Five SNPs were confirmed in a combined analysis of both replication cohorts but showed different association patterns in subgroup analyses. In an unweighted polygenic risk score (PRS), the risk for metformin side effects increased with the number of risk alleles. Intronic SNPs in the OCT cluster contribute to the development of metformin side effects in individuals with T2DM and in women with PCOS and are therefore of interest for personalized therapy options.

Find related publications in this database (using NLM MeSH Indexing)

Female - administration & dosage

Humans - administration & dosage

Polymorphism, Single Nucleotide - administration & dosage

Metformin - adverse effects

Diabetes Mellitus, Type 2 - drug therapy, genetics

Drug-Related Side Effects and Adverse Reactions - administration & dosage

Introns - genetics

Membrane Transport Proteins - administration & dosage

Polycystic Ovary Syndrome - drug therapy, genetics

Find related publications in this database (Keywords)

metformin

side effects

transporter proteins

single nucleotide polymorphisms

polygenic risk score

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