Common variants in 22 genes gegulate response to Metformin intervention in children with obesity: a pharmacogenetic study of a randomized controlled trial
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|Title:||Common variants in 22 genes gegulate response to Metformin intervention in children with obesity: a pharmacogenetic study of a randomized controlled trial
|Author:||Anguita Ruiz, Augusto
Pastor Villaescusa, Belén
Leis Trabazo, María Rosaura
Vázquez Cobela, Rocío
Latorre Millán, Miriam
Cañete, M. Dolores
Caballero Villarraso, Javier
Aguilera, Concepción M.
|Affiliation:||Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría
|Subject:||Metformin | Obesity | Pediatrics | SNP | Pharmacogenetics | Clinical trials ||
|Date of Issue:||2019
|Citation:||Anguita-Ruiz, A.; Pastor-Villaescusa, B.; Leis, R.; Bueno, G.; Hoyos, R.; Vázquez-Cobela, R.; Latorre-Millán, M.; Cañete, M.D.; Caballero-Villarraso, J.; Gil, Á.; Cañete, R.; Aguilera, C.M. Common Variants in 22 Genes Regulate Response to Metformin Intervention in Children with Obesity: A Pharmacogenetic Study of a Randomized Controlled Trial. J. Clin. Med. 2019, 8, 1471.
|Abstract:||Metformin is a first-line oral antidiabetic agent that has shown additional effects in treating obesity and metabolic syndrome. Inter-individual variability in metformin response could be partially explained by the genetic component. Here, we aimed to test whether common genetic variants can predict the response to metformin intervention in obese children. The study was a multicenter and double-blind randomized controlled trial that was stratified according to sex and pubertal status in 160 children with obesity. Children were randomly assigned to receive either metformin (1g/d) or placebo for six months after meeting the defined inclusion criteria. We conducted a post hoc genotyping study in 124 individuals (59 placebo, 65 treated) comprising finally 231 genetic variants in candidate genes. We provide evidence for 28 common variants as promising pharmacogenetics regulators of metformin response in terms of a wide range of anthropometric and biochemical outcomes, including body mass index (BMI) Z-score, and glucose, lipid, and inflammatory traits. Although no association remained statistically significant after multiple-test correction, our findings support previously reported variants in metformin transporters or targets as well as identify novel and promising loci, such as the ADYC3 and the BDNF genes, with plausible biological relation to the metformin’s action mechanism. Trial Registration: Registered on the European Clinical Trials Database (EudraCT, ID: 2010-023061-21) on 14 November 2011 (URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-023061-21/ES).|
|Rights:||© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Except where otherwise noted, this item's license is described as © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).