PMID- 29979413
OWN - NLM
STAT- MEDLINE
DCOM- 20180717
LR  - 20221207
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 97
IP  - 27
DP  - 2018 Jul
TI  - Genetic polymorphisms of organic cation transporter 1 (OCT1) and responses to 
      metformin therapy in individuals with type 2 diabetes: A systematic review.
PG  - e11349
LID - 10.1097/MD.0000000000011349 [doi]
LID - e11349
AB  - BACKGROUND: Metformin is one of the most commonly used drugs for the treatment of 
      type 2 diabetes mellitus (T2DM). Despite its widespread use, there are 
      considerable interindividual variations in metformin response, with about 35% of 
      patients failing to achieve initial glycemic control. These variabilities that 
      reflect phenotypic differences in drug disposition and action may indeed be due 
      to polymorphisms in genes that regulate pharmacokinetics and pharmacodynamics of 
      metformin. Moreover, interethnic differences in drug responses in some cases 
      correspond to substantial differences in the frequencies of the associated 
      pharmacogenomics risk allele. AIM: This study aims to highlight and summarize the 
      overall effects of organic cation transporter 1(OCT1) polymorphisms on 
      therapeutic responses to metformin and to evaluate the potential role of such 
      polymorphisms in interethnic differences in metformin therapy. METHODS: We 
      conducted a systematic review according to the Preferred Reporting Items for 
      Systematic Review and Meta-Analysis (PRISMA) guidelines. We searched for 
      PubMed/MEDLINE, Embase, and CINAHL, relevant studies reporting the effects of 
      OCT1 polymorphisms on metformin therapy in T2DM individuals. Data were extracted 
      on study design, population characteristics, relevant polymorphisms, measure of 
      genetic association, and outcomes. The presence of gastrointestinal side effects, 
      glycated hemoglobin A1 (HbA1c) levels, fasting plasma glucose (FPG), and 
      postprandial plasma glucose (PPG) concentrations after treatment with metformin 
      were chosen as measures of the metformin responses. This systematic review 
      protocol was registered with the International Prospective Register of Systematic 
      Reviews (PROSPERO). RESULTS: According to the data extracted, a total of 34 OCT1 
      polymorphisms were identified in 10 ethnic groups. Significant differences in the 
      frequencies of common alleles were observed among these groups. Met408Val 
      (rs628031) variant was the most extensively explored with metformin responses. 
      Although some genotypes and alleles have been associated with deleterious effects 
      on metformin response, others indeed, exhibited positive effects. CONCLUSION: 
      Genetic effects of OCT1 polymorphisms on metformin responses were population 
      specific. Further investigations in other populations are required to set 
      ethnicity-specific reference for metformin responses and to obtain a solid basis 
      to design personalized therapeutic approaches for T2DM treatment.
FAU - Mofo Mato, Edith Pascale
AU  - Mofo Mato EP
AD  - Molecular and Clinical Pharmacology Research Laboratory, Department of 
      Pharmacology, Discipline of Pharmaceutical Sciences, School of Health Sciences, 
      University of KwaZulu-Natal, Durban, South Africa Laboratory of Public Health 
      Research Biotechnology (LAPHER-Biotech) Laboratory of Molecular Medicine and 
      Metabolism (LMMM), Biotechnology Centre, University of Yaounde I, Yaounde, 
      Cameroon Cardio-Metabolic Research Group (CMRG), Department of Physiological 
      Sciences, Stellenbosch University, Stellenbosch, South Africa.
FAU - Guewo-Fokeng, Magellan
AU  - Guewo-Fokeng M
FAU - Essop, M Faadiel
AU  - Essop MF
FAU - Owira, Peter Mark Oroma
AU  - Owira PMO
LA  - eng
PT  - Journal Article
PT  - Review
PT  - Systematic Review
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Octamer Transcription Factor-1)
RN  - 0 (POU2F1 protein, human)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Alleles
MH  - Blood Glucose/drug effects
MH  - Diabetes Mellitus, Type 2/drug therapy/*genetics
MH  - Female
MH  - Genotype
MH  - Glycated Hemoglobin/drug effects
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Male
MH  - Metformin/*therapeutic use
MH  - Octamer Transcription Factor-1/*genetics
MH  - Polymorphism, Single Nucleotide
PMC - PMC6076123
COIS- The authors have no funding and no conflicts of interest to disclose.
EDAT- 2018/07/07 06:00
MHDA- 2018/07/18 06:00
PMCR- 2018/07/06
CRDT- 2018/07/07 06:00
PHST- 2018/07/07 06:00 [entrez]
PHST- 2018/07/07 06:00 [pubmed]
PHST- 2018/07/18 06:00 [medline]
PHST- 2018/07/06 00:00 [pmc-release]
AID - 00005792-201807060-00040 [pii]
AID - MD-D-18-01803 [pii]
AID - 10.1097/MD.0000000000011349 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2018 Jul;97(27):e11349. doi: 10.1097/MD.0000000000011349.