Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by

Aged Alleles Diabetes Mellitus, Type 2 / drug therapy Drug Hypersensitivity / genetics Equilibrative Nucleoside Transport Proteins / genetics Female Gastrointestinal Diseases / chemically induced Genetic Association Studies Humans Hypoglycemic Agents / adverse effects Male Metformin / adverse effects Middle Aged Organic Cation Transporter 1 / genetics Polymorphism, Single Nucleotide Risk Factors

Journal

Diabetes care
ISSN: 1935-5548
Titre abrégé: Diabetes Care
Pays: United States
ID NLM: 7805975

Informations de publication

Date de publication:
06 2019
Historique:
received: 19 10 2018
accepted: 11 02 2019
pubmed: 20 3 2019
medline: 26 3 2020
entrez: 20 3 2019
Statut: ppublish

Résumé

Gastrointestinal adverse effects occur in 20-30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation in 5-10% of the cases. Gastrointestinal intolerance may reflect localized high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects. The study included 286 severe metformin-intolerant and 1,128 metformin-tolerant individuals from the IMI DIRECT (Innovative Medicines Initiative: DIabetes REsearCh on patient straTification) consortium. We assessed the association of patient characteristics, concomitant medication, and the burden of mutations in the Women ( These results suggest that intestinal metformin transporters and concomitant medications play an important role in the gastrointestinal adverse effects of metformin.

Identifiants

DOI: 10.2337/dc18-2182 PMID: 30885951
pubmed: 30885951
pii: dc18-2182
doi: 10.2337/dc18-2182
doi:

Substances chimiques

Equilibrative Nucleoside Transport Proteins 0
Hypoglycemic Agents 0
Organic Cation Transporter 1 0
SLC29A4 protein, human 0
Metformin 9100L32L2N

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1027-1033

Subventions

Organisme : Wellcome Trust
ID : 102820/Z/13/Z
Pays : United Kingdom

Investigateurs

C Jennison (C)
B Ehrhardt (B)
P Baum (P)
C Schoelsch (C)
J I Freijer (JI)
R Grempler (R)
U Graefe-Mody (U)
A M Hennige (AM)
C Dings (C)
T Lehr (T)
N Scherer (N)
I Sihinecich (I)
F Pattou (F)
V Raverdi (V)
R Caiazzo (R)
F Torres (F)
H Verkindt (H)
A Mari (A)
A Tura (A)
T Giorgino (T)
R Bizzotto (R)
P Froguel (P)
A Bonneford (A)
M Canouil (M)
V Dhennin (V)
C A Brorsson (CA)
S Brunak (S)
F De Masi (F)
V Gudmundsdóttir (V)
H K Pedersen (HK)
K Banasik (K)
E Thomas (E)
W Sackett (W)
H Staerfeldt (H)
A T Lundgaard (AT)
B Nilsson (B)
A M Nielsen (AM)
G Mazzoni (G)
T Karaderi (T)
S Rasmussen (S)
J Johansen (J)
R L Allesøe (RL)
A Fritsche (A)
B Thorand (B)
J Adamski (J)
H Grallert (H)
M Haid (M)
S Sharma (S)
M Troll (M)
J Adam (J)
J Ferrer (J)
P Froguel (P)
R G Eriksen (RG)
G Frost (G)
R Haussler (R)
M-G Hong (MG)
J M Schwenk (JM)
M Uhlen (M)
C Nicolay (C)
I Pavo (I)
B Steckel-Hamann (B)
M K Thomas (MK)
K Adragni (K)
H Wu (H)
L M 't Hart (LM)
R C Roderick (RC)
N van Leeuwen (N)
K F Dekkers (KF)
F Frau (F)
J Gassenhuber (J)
B Jablonka (B)
P Musholt (P)
H Ruetten (H)
J Tillner (J)
T Baltauss (T)
O Bernard (O)
N Poenaru (N)
M de Preville (M)
M Rodriquez (M)
K H Arumugam (KH)
L Allin (L)
T Engelbrechtsen (T)
T H Hansen (TH)
A Hansen (A)
A Forman (A)
O Jonsson (O)
A Pedersen (A)
J K Dutta (JK)
H Vogt (H)
M Vestergaard (M)
T Laakso (T)
T Kokkola (T)
P W Kuulasmaa (PW)
G N Franks (GN)
H Giordano (H)
H Pomares-Millan (H)
P Fitipaldi (P)
M Mutie (M)
M Klintenberg (M)
L Bergstrom (L)
M Groop (M)
N Ridderstrale (N)
H A Atabaki Pasdar (HA)
A J Deshmukh (AJ)
D Heggie (D)
D Wake (D)
I McEvoy (I)
M McVittie (M)
A T Walker (AT)
A V Hattersley (AV)
A G Hill (AG)
T J Jones (TJ)
M H McDonald (MH)
R Perry (R)
M Nice (M)
C E Hudson (CE)
E T Thorne (ET)
A Dermitzakis (A)
L Viñuela (L)
H Cabrelli (H)
A Y Loftus (AY)
L Dawed (L)
I M Donnelly (IM)
E R Forgie (ER)
C N Pearson (CN)
A A Palmer (AA)
R W Brown (RW)
A Koivula (A)
M Wesolowska-Andersen (M)
N Abdalla (N)
J McRobert (J)
J Fernandez (J)
M Kaye (M)
A Mourby (A)
M I Mahajan (MI)
N McCarthy (N)
H Shah (H)
Y Teare (Y)
N Jiao (N)
S Robertson (S)
R W Gough (RW)
A D Holl (AD)
F Koopman (F)
J W Rutters (JW)
L Beulens (L)
A D Groeneveld (AD)
J D Koopman (JD)
E L Bell (EL)
None Thomas
B Whitcher (B)

Informations de copyright

© 2019 by the American Diabetes Association.

Auteurs

Adem Y Dawed (AY)

Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, U.K.
ORCID: 0000-0003-0224-2428

Kaixin Zhou (K)

Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, U.K.

Nienke van Leeuwen (N)

Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.

Anubha Mahajan (A)

Wellcome Centre for Human Genetics, University of Oxford, Oxford, U.K.

Neil Robertson (N)

Wellcome Centre for Human Genetics, University of Oxford, Oxford, U.K.
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, U.K.

Robert Koivula (R)

Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, U.K.
Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Skåne University Hospital, Malmö, Lund University, Malmö, Sweden.

Petra J M Elders (PJM)

Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, the Netherlands.

Simone P Rauh (SP)

Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, the Netherlands.

Angus G Jones (AG)

Institute of Clinical and Biological Sciences, University of Exeter Medical School, Exeter, U.K.

Reinhard W Holl (RW)

Institute of Epidemiology and Medical Biometry (ZIBMT), University of Ulm, Ulm, Germany, and German Center for Diabetes Research (DZD), München-Neuherberg, Germany.

Julia C Stingl (JC)

Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany.

Paul W Franks (PW)

Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Skåne University Hospital, Malmö, Lund University, Malmö, Sweden.
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
ORCID: 0000-0002-0520-7604

Mark I McCarthy (MI)

Wellcome Centre for Human Genetics, University of Oxford, Oxford, U.K.
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, U.K.
Oxford National Institute for Health Research Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, U.K.

Leen M 't Hart (LM)

Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Section of Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.

Ewan R Pearson (ER)

ORCID: 0000-0001-9237-8585

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Allèles › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Diabète de type 2 › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Troubles dus à des produits chimiques › Effets secondaires indésirables des médicaments › Hypersensibilité médicamenteuse › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Protéines transporteurs de solutés › Transporteurs équilibrants de nucléosides › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Études d'associations génétiques › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hypoglycémiants › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Composés chimiques organiques › Amidines › Guanidines › Biguanides › Metformine › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Protéines transporteurs de solutés › Transporteurs de cations organiques › Transporteur-1 de cations organiques › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Variation in the Plasma Membrane Monoamine...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Variation in the Plasma Membrane Monoamine...