Background: Metformin is the drug of first choice in people newly diagnosed with type 2 diabetes. Most patients respond to metformin monotherapy, but many others remain uncontrolled even at maximal doses. Although non-adherence is a major contributor to non-response, genetic polymorphisms of organic cation transporters play an important role in clinical response. We hypothesize that genetic variants are partly responsible for non-response. Objective: This study aims to determine the allele and genotype frequencies of three single nucleotide polymorphisms (SNPs; ATM rs11212617, SLC22A1 rs594709 and SLC47A1 rs2289669) most commonly associated with failure to respond to metformin. Setting: Ten primary health care facilities in the North Central Regional Health Authority region of Trinidad. Patients: The study population will include 216 patients with diabetes adherent to metformin monotherapy for at least three months. Methods: Following a 12-hour overnight fast, blood samples will be taken to measure fasting insulin and HbA1c. DNA would be isolated and PCR will be used to determine the allele and genotype frequencies of these three SNPs in adherent diabetic patients. DNA samples will be stored for future sequencing of these three genes to determine whether other, possibly novel, mutations are associated with poor metformin response in Trinidad. Clinical Significance: This study will highlight the prevalence of these polymorphisms in our population. Should an association be found between the polymorphisms tested and glycemic control in adherent patients on metformin monotherapy, this will have implications for further research on medication initiation in newly diagnosed patients with diabetes in Trinidad.
Background: Metformin is the drug of first choice in people newly diagnosed with type 2 diabetes. Most patients respond to metformin monotherapy, but many others remain uncontrolled even at maximal doses. Although non-adherence is a major contributor to non-response, genetic polymorphisms of organic cation transporters play an important role in clinical response. We hypothesize that genetic variants are partly responsible for non-response. Objective: This study aims to determine the allele and genotype frequencies of three single nucleotide polymorphisms (SNPs; ATMrs11212617, SLC22A1rs594709 and SLC47A1rs2289669) most commonly associated with failure to respond to metformin. Setting: Ten primary health care facilities in the North Central Regional Health Authority region of Trinidad. Patients: The study population will include 216 patients with diabetes adherent to metformin monotherapy for at least three months. Methods: Following a 12-hour overnight fast, blood samples will be taken to measure fasting insulin and HbA1c. DNA would be isolated and PCR will be used to determine the allele and genotype frequencies of these three SNPs in adherent diabeticpatients. DNA samples will be stored for future sequencing of these three genes to determine whether other, possibly novel, mutations are associated with poor metformin response in Trinidad. Clinical Significance: This study will highlight the prevalence of these polymorphisms in our population. Should an association be found between the polymorphisms tested and glycemic control in adherent patients on metformin monotherapy, this will have implications for further research on medication initiation in newly diagnosed patients with diabetes in Trinidad.
Authors: Garry G Graham; Jeroen Punt; Manit Arora; Richard O Day; Matthew P Doogue; Janna K Duong; Timothy J Furlong; Jerry R Greenfield; Louise C Greenup; Carl M Kirkpatrick; John E Ray; Peter Timmins; Kenneth M Williams Journal: Clin Pharmacokinet Date: 2011-02 Impact factor: 6.447
Authors: Kaixin Zhou; Celine Bellenguez; Chris C A Spencer; Amanda J Bennett; Ruth L Coleman; Roger Tavendale; Simon A Hawley; Louise A Donnelly; Chris Schofield; Christopher J Groves; Lindsay Burch; Fiona Carr; Amy Strange; Colin Freeman; Jenefer M Blackwell; Elvira Bramon; Matthew A Brown; Juan P Casas; Aiden Corvin; Nicholas Craddock; Panos Deloukas; Serge Dronov; Audrey Duncanson; Sarah Edkins; Emma Gray; Sarah Hunt; Janusz Jankowski; Cordelia Langford; Hugh S Markus; Christopher G Mathew; Robert Plomin; Anna Rautanen; Stephen J Sawcer; Nilesh J Samani; Richard Trembath; Ananth C Viswanathan; Nicholas W Wood; Lorna W Harries; Andrew T Hattersley; Alex S F Doney; Helen Colhoun; Andrew D Morris; Calum Sutherland; D Grahame Hardie; Leena Peltonen; Mark I McCarthy; Rury R Holman; Colin N A Palmer; Peter Donnelly; Ewan R Pearson Journal: Nat Genet Date: 2010-12-26 Impact factor: 38.330
Authors: Nira Roopnarinesingh; Nancyellen Brennan; Claude Khan; Paul W Ladenson; Felicia Hill-Briggs; Rita Rastogi Kalyani Journal: BMC Health Serv Res Date: 2015-09-19 Impact factor: 2.655
Authors: Nadia R Bennett; Damian K Francis; Trevor S Ferguson; Anselm J M Hennis; Rainford J Wilks; Eon Nigel Harris; Marlene M Y MacLeish; Louis W Sullivan Journal: Int J Equity Health Date: 2015-02-25