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Organic cation transporter 1 polymorphisms predict the metabolic response to metformin in women with the polycystic ovary syndrome.
MedLine Citation:
PMID:  20660041     Owner:  NLM     Status:  In-Process    
CONTEXT: The determinants of the variability in the clinical response to metformin in women with the polycystic ovary syndrome (PCOS) are enigmatic. Organic cation transporter 1 (OCT1) plays a trigger role in the hepatic uptake of metformin. In cellular studies, it was recently shown that seven polymorphisms of OCT1 exhibit reduced transport of metformin. It is noteworthy that four of the seven variants, R61C (C>T), G401S (G>A), G465R (G>A), and 420del, are present in individuals of European descent. OBJECTIVE: The aim was testing the hypothesis that polymorphisms in OCT1 may contribute to the variability in the response to metformin in PCOS. DESIGN AND SETTING: We conducted a prospective study at an academic hospital. PATIENTS: We studied 150 Italian PCOS patients aged 18-45 yr. INTERVENTIONS: We administered two oral doses of metformin per day for 6 months. MAIN OUTCOME MEASURES: We measured the genotype distribution of R61C, G401S, G465R, and 420del and the influence of genotypes on response to metformin. RESULTS: Eighty-four PCOS women had the reference allele at all four positions and were classified as "References," whereas 66 PCOS women carried at least one copy of the four polymorphisms (52 carried one polymorphism, 13 carried two polymorphisms, and one carried three polymorphisms) and were classified as "Variants." Only the References reduced their total cholesterol [-14 mg/dl (-22 to -5); P = 0.002] and triglycerides [-17 mg/dl (-29 to -5); P = 0.008]. Insulin(AUC) decreased in References and in Variants carrying one polymorphism, but it did not change in Variants carrying two or more polymorphisms. CONCLUSIONS: Genetic variation in OCT1 may be associated with heterogeneity in the metabolic response to metformin in women with PCOS.
Alessandra Gambineri; Federica Tomassoni; Daniela Ibarra Gasparini; Antonio Di Rocco; Vilma Mantovani; Uberto Pagotto; Paola Altieri; Stefania Sanna; Anna Maria Fulghesu; Renato Pasquali
Publication Detail:
Type:  Journal Article     Date:  2010-07-21
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E204-8     Citation Subset:  AIM; IM    
Division of Endocrinology, Department of Clinical Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
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