Organic Cation Transporter 1 Polymorphisms Predict the Metabolic Response to Metformin in Women with the Polycystic Ovary Syndrome (original) (raw)

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1Division of Endocrinology (A.G., F.T., D.I.G., A.D.R., V.M., U.P., P.A., R.P.), Department of Clinical Medicine, Centre for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy;

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1Division of Endocrinology (A.G., F.T., D.I.G., A.D.R., V.M., U.P., P.A., R.P.), Department of Clinical Medicine, Centre for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy;

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1Division of Endocrinology (A.G., F.T., D.I.G., A.D.R., V.M., U.P., P.A., R.P.), Department of Clinical Medicine, Centre for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy;

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1Division of Endocrinology (A.G., F.T., D.I.G., A.D.R., V.M., U.P., P.A., R.P.), Department of Clinical Medicine, Centre for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy;

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1Division of Endocrinology (A.G., F.T., D.I.G., A.D.R., V.M., U.P., P.A., R.P.), Department of Clinical Medicine, Centre for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy;

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1Division of Endocrinology (A.G., F.T., D.I.G., A.D.R., V.M., U.P., P.A., R.P.), Department of Clinical Medicine, Centre for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy;

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1Division of Endocrinology (A.G., F.T., D.I.G., A.D.R., V.M., U.P., P.A., R.P.), Department of Clinical Medicine, Centre for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy;

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2Unit of Gynecology, Obstetrics, and Physiopathology of Human Reproduction (S.S., A.M.F.), University of Cagliari, 09124 Cagliari, Italy

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2Unit of Gynecology, Obstetrics, and Physiopathology of Human Reproduction (S.S., A.M.F.), University of Cagliari, 09124 Cagliari, Italy

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1Division of Endocrinology (A.G., F.T., D.I.G., A.D.R., V.M., U.P., P.A., R.P.), Department of Clinical Medicine, Centre for Applied Biomedical Research, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy;

*Address all correspondence and requests for reprints to: Renato Pasquali, M.D., Division of Endocrinology, Department of Clinical Medicine, S. Orsola-Malpighi Hospital, University Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, Italy.

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Received:

20 January 2010

Published:

01 October 2010

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Alessandra Gambineri, Federica Tomassoni, Daniela Ibarra Gasparini, Antonio Di Rocco, Vilma Mantovani, Uberto Pagotto, Paola Altieri, Stefania Sanna, Anna Maria Fulghesu, Renato Pasquali, Organic Cation Transporter 1 Polymorphisms Predict the Metabolic Response to Metformin in Women with the Polycystic Ovary Syndrome, The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 10, 1 October 2010, Pages E204–E208, https://doi.org/10.1210/jc.2010-0145
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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]. InsulinAUC 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.

Copyright © 2010 by The Endocrine Society

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