Metformin resistance alleles in polycystic ovary syndrome: pattern and association with glucose metabolism

Insulin-sensitizer treatment with metformin is common in polycystic ovary syndrome (PCOS). OCT alleles were investigated in PCOS patients to identify genetic bad responders' and nonresponders' to metformin including their possible effects on glucose metabolism without treatment. We genotyped eight SNPs in OCT1, OCT2 and ATM genes in 676 women with PCOS and 90 control women, we also measured oral glucose tolerance tests prior to treatment. Nonfunctional alleles were present in 29.8% and low-functional alleles in 57.9% of our PCOS cohort. OCT variants were significantly associated with elevated baseline and glucose-induced C-peptide levels in PCOS. Metformin bad responders or nonresponders based on OCT genotypes might be relevant in clinical practice - their modulation of metformin pharmacokinetics and pharmacodynamics and metformin-independent glucose effects remain to be elucidated. Original submitted 7 June 2013; Revision submitted 28 October 2013