PMID- 30433870
OWN - NLM
STAT- MEDLINE
DCOM- 20190617
LR  - 20221207
IS  - 2363-8915 (Electronic)
IS  - 2363-8915 (Linking)
VI  - 33
IP  - 4
DP  - 2018 Dec 19
TI  - Lack of effect of the SLC47A1 and SLC47A2 gene polymorphisms on the glycemic 
      response to metformin in type 2 diabetes mellitus patients.
PG  - 175-185
LID - 10.1515/dmpt-2018-0030 [doi]
AB  - Background This work aimed to evaluate the influence of single nucleotide 
      polymorphisms (SNPs) in the SLC47A1 (922-158G>A; rs2289669) and SLC47A2 (-130G>A; 
      rs12943590) genes on the relative change in HbA1c in type 2 diabetes mellitus 
      (T2DM) patients of South India who are taking metformin as monotherapy. It also 
      aims to study the effects of these SNPs on the dose requirement of metformin for 
      glycemic control and the adverse effects of metformin. Methods Diabetes patients 
      on metformin monotherapy were recruited based on the eligibility criteria 
      (n=105). DNA was extracted and genotyping was performed with a real-time PCR 
      system using TaqMan(R) SNP genotyping assay method. The HbA1c levels were measured 
      using Bio-Rad D-10 Hemoglobin Analyzer. Results After adjusting for multiple 
      comparisons (Bonferroni correction) the difference found in the glycemic response 
      between the "GG" genotype and "AG/AA" genotype groups of the SLC47A2 gene was not 
      significant (p=0.027; which was greater than the critical value of 0.025). 
      Patients with "GG" genotype showed a 5.5% decrease in HbA1c from baseline 
      compared to those with the "AG/AA" genotype (0.1% increase). The SNP in the 
      SLC47A1 gene also did not influence the glycemic response to metformin (p=0.079). 
      The median dose requirements based on the genotypes of the rs12943590 variant 
      (p=0.357) or rs2289669 variant (p=0.580) were not significantly different. 
      Similarly, there was no significant difference in the occurrence of adverse 
      effects across the genotypes in both the SLC47A1 (p=0.615) and SLC47A2 (p=0.309) 
      genes. Conclusions The clinical response to metformin was not associated with the 
      SNPs in the SLC47A1 and SLC47A2 genes coding for the multidrug and toxin 
      extrusion protein (MATE) transporters. Furthermore, the studied SNPs had no 
      influence on the dose requirement or adverse effects of metformin.
FAU - Raj, Gerard Marshall
AU  - Raj GM
AUID- ORCID: 0000-0001-7499-7219
AD  - Department of Pharmacology, Sri Venkateshwaraa Medical College Hospital and 
      Research Centre (SVMCH & RC), Pondy-Villupuram Main Road, Ariyur, Puducherry 
      605102, India.
FAU - Mathaiyan, Jayanthi
AU  - Mathaiyan J
AD  - Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical 
      Education and Research (JIPMER), Puducherry, India.
FAU - Wyawahare, Mukta
AU  - Wyawahare M
AD  - Department of General Medicine, Jawaharlal Institute of Postgraduate Medical 
      Education and Research (JIPMER), Puducherry, India.
FAU - Priyadarshini, Rekha
AU  - Priyadarshini R
AD  - Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical 
      Education and Research (JIPMER), Puducherry, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Drug Metab Pers Ther
JT  - Drug metabolism and personalized therapy
JID - 101653409
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Organic Cation Transport Proteins)
RN  - 0 (SLC47A1 protein, human)
RN  - 0 (SLC47A2 protein, human)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Blood Glucose/analysis
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy/genetics
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Genotype
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Male
MH  - Metformin/administration & dosage/adverse effects/*therapeutic use
MH  - Middle Aged
MH  - Organic Cation Transport Proteins/*genetics
MH  - *Polymorphism, Single Nucleotide
MH  - Prospective Studies
OTO - NOTNLM
OT  - metformin
OT  - multidrug and toxin extrusion proteins
OT  - single nucleotide polymorphism
OT  - solute carrier family 47 member 1 (SLC47A1)
OT  - solute carrier family 47 member 2 (SLC47A2)
EDAT- 2018/11/16 06:00
MHDA- 2019/06/18 06:00
CRDT- 2018/11/16 06:00
PHST- 2018/09/25 00:00 [received]
PHST- 2018/10/26 00:00 [accepted]
PHST- 2018/11/16 06:00 [pubmed]
PHST- 2019/06/18 06:00 [medline]
PHST- 2018/11/16 06:00 [entrez]
AID - /j/dmdi.ahead-of-print/dmpt-2018-0030/dmpt-2018-0030.xml [pii]
AID - 10.1515/dmpt-2018-0030 [doi]
PST - ppublish
SO  - Drug Metab Pers Ther. 2018 Dec 19;33(4):175-185. doi: 10.1515/dmpt-2018-0030.