title: Metformin resistance alleles in polycystic ovary syndrome: pattern and association with glucose metabolism.
abstract: 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.
authors.affiliation: Division of Endocrinology & Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
authors.forename: Natascha
authors.initials: N
authors.lastname: Schweighofer
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lerchbaum
authors.forename: Olivia
authors.initials: O
authors.lastname: Trummer
authors.forename: Verena
authors.initials: V
authors.lastname: Schwetz
authors.forename: Thomas
authors.initials: T
authors.lastname: Pieber
authors.forename: Barbara
authors.initials: B
authors.lastname: Obermayer-Pietsch
mesh_terms: D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D002096:C-Peptide / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008687:Metformin / Q000008:administration & dosage; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D027702:Organic Cation Transporter 1 / Q000235:genetics*; D000075102:Organic Cation Transporter 2; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide
chemical_list: D002096:C-Peptide; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D000075102:Organic Cation Transporter 2; C491013:SLC22A2 protein, human; D008687:Metformin; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D005947:Glucose