6533b7d7fe1ef96bd1267b79

RESEARCH PRODUCT

Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin

Kathleen M. GiacominiAdriaan KooyCoen D.a. StehouwerMetgen InvestigatorsValdis PiragsValdis PiragsDaniel M. RotroffIvan TkáčHuan-chieh ChienMichael J. WagnerShiro MaedaFederico InnocentiJoline W.j. BeulensJoline W.j. BeulensMonique M. HeddersonEric L. SeiserSook Wah YeeBruno H. StrickerAccord InvestigatorsAccord InvestigatorsJozef ŽIdzikLeen M 'T HartLeen M 'T HartRury R. HolmanAlison A. Motsinger-reifJose C. FlorezAlbert HofmanMattijs OutAlbert M. LevinChristopher J. GrovesMichiaki KuboLongyang WuCatherine E. De KeyserEwan R. PearsonLisa LogieCalum SutherlandSabina SemizSabina SemizTanja DujicTanja DujicJohn S. WitteAmanda J. BennettKathleen A. JablonskiLinda ZaharenkoNienke Van LeeuwenLing ChenDpp InvestigatorsRoger TavendaleRuth L. ColemanAmber A. Van Der HeijdenColin N. A. PalmerJanis KlovinsMartin JavorskýRon H.n. Van SchaikMark I. MccarthyMark I. MccarthyMark I. MccarthyL. Keoki WilliamsKaixin Zhou

subject

Blood Glucose0301 basic medicinemedicine.medical_specialtyendocrine system diseasesGenome-wide association studyType 2 diabetesPolymorphism Single NucleotideWhite PeopleBody Mass Index03 medical and health sciencesQuantitative Trait HeritableInternal medicineDiabetes mellitusGeneticsmedicineHumansHypoglycemic AgentsAlleleGlycemicGlucose Transporter Type 2Glycated HemoglobinbiologyGlucose transporternutritional and metabolic diseasesmedicine.diseaseMetformin3. Good healthMetformin030104 developmental biologyEndocrinologyDiabetes Mellitus Type 2biology.proteinGLUT2Genome-Wide Association Studymedicine.drug

description

Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear(1). Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 x 10(-14)) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry. rs8192675 was the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. Among obese individuals, C-allele homozygotes at rs8192675 had a 0.33% (3.6 mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes. This was about half the effect seen with the addition of a DPP-4 inhibitor, and equated to a dose difference of 550 mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine.

yearjournalcountryeditionlanguage
2016-09-01
https://hdl.handle.net/1887/96245