Cindy T Pau1, Kai I Cheang2, Bhavi P Modi2, Thushiga Kasippillai1,3, Candace C Keefe1, Maria Shulleeta2, William S Evans4, Lubna Pal5, Jerome F Strauss2, John E Nestler2, Corrine K Welt1,6. 1. Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA. 2. Departments of Obstetrics & Gynecology, Internal Medicine & Human & Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA. 3. VU University Medical Center, Amsterdam, The Netherlands. 4. Division of Endocrinology, University of Virginia, Charlottesville, VA 22908, USA. 5. Department of Obstetrics & Gynecology, Yale University, New Haven, CT 06520, USA. 6. Division of Endocrinology, Metabolism & Diabetes, University of Utah, Salt Lake City, UT 84112, USA.
Abstract
AIMS: Variants in genes encoding metformin transport proteins and the ATM gene are associated with metformin response. We hypothesized that these gene variants contribute to variable metformin treatment response in polycystic ovary syndrome. MATERIALS & METHODS: The discovery cohort (n = 38) was studied in an open-label study. Results were replicated in two additional cohorts (n = 26 and n = 131). Response was assessed after 3-6 months of treatment with metformin extended-release 1500-2000 mg/day. RESULTS: The rs683369 variant was associated with less weight loss in the discovery cohort (p = 0.003), but these results were not replicated (p = 0.8). There were no differences in glucose parameters, testosterone levels or ovulatory frequency as a function of genotype. CONCLUSION: Variants in organic ion transporters do not explain the variable metformin response in polycystic ovary syndrome.
AIMS: Variants in genes encoding metformin transport proteins and the ATM gene are associated with metformin response. We hypothesized that these gene variants contribute to variable metformin treatment response in polycystic ovary syndrome. MATERIALS & METHODS: The discovery cohort (n = 38) was studied in an open-label study. Results were replicated in two additional cohorts (n = 26 and n = 131). Response was assessed after 3-6 months of treatment with metformin extended-release 1500-2000 mg/day. RESULTS: The rs683369 variant was associated with less weight loss in the discovery cohort (p = 0.003), but these results were not replicated (p = 0.8). There were no differences in glucose parameters, testosterone levels or ovulatory frequency as a function of genotype. CONCLUSION: Variants in organic ion transporters do not explain the variable metformin response in polycystic ovary syndrome.
Authors: Verónica Yumiceba; Andrés López-Cortés; Andy Pérez-Villa; Iván Yumiseba; Santiago Guerrero; Jennyfer M García-Cárdenas; Isaac Armendáriz-Castillo; Patricia Guevara-Ramírez; Paola E Leone; Ana Karina Zambrano; César Paz-Y-Miño Journal: Front Endocrinol (Lausanne) Date: 2020-10-26 Impact factor: 5.555