RT Journal Article
T1 Common Variants in 22 Genes Regulate Response to Metformin Intervention in Children with Obesity: A Pharmacogenetic Study of a Randomized Controlled Trial.
A1 Anguita-Ruiz, Augusto
A1 Pastor-Villaescusa, Belén
A1 Leis, Rosaura
A1 Bueno, Gloria
A1 Hoyos, Raúl
A1 Vázquez-Cobela, Rocío
A1 Latorre-Millán, Miriam
A1 Cañete, M Dolores
A1 Caballero-Villarraso, Javier
A1 Gil, Ángel
A1 Cañete, Ramón
A1 Aguilera, Concepción M
K1 SNP
K1 clinical trials
K1 metformin
K1 obesity
K1 pediatrics
K1 pharmacogenetics
AB 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).
SN 2077-0383
YR 2019
FD 2019-09-16
LK https://hdl.handle.net/10668/28151
UL https://hdl.handle.net/10668/28151
LA en
DS RISalud
RD Apr 8, 2025