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Lack of effect of the SLC47A1 and SLC47A2 gene polymorphisms on the glycemic response to metformin in type 2 diabetes mellitus patients

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Published/Copyright: November 15, 2018
Drug Metabolism and Personalized Therapy
From the journal Drug Metabolism and Personalized Therapy Volume 33 Issue 4

Abstract

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® 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.

Keywords: metformin; multidrug and toxin extrusion proteins; single nucleotide polymorphism; solute carrier family 47 member 1 (SLC47A1); solute carrier family 47 member 2 (SLC47A2)
Corresponding author: Dr. Gerard Marshall Raj, Department of Pharmacology, Sri Venkateshwaraa Medical College Hospital and Research Centre (SVMCH & RC), Pondy-Villupuram Main Road, Ariyur, Puducherry 605102, India, Phone: +91-9245124616, +91-413-2255168

Acknowledgments

We wish to thank Dr. Saranya Vilvanathan, Dr. Neel Shah, Dr. Radhika, Dr. Stanley, Dr. Jose Francis and Dr. Abialbon Paul (Department of Pharmacology, JIPMER, Puducherry, India) for giving us valuable suggestions while designing the study. We would like to express our sincere gratitude to Dr. Srinivas Rao, Dr. Sunitha, Dr. Neel Shah, Dr. C. Indumathi, Mr. Rajan, Ms. Tamijarassy and Ms. Immaculate (Department of Pharmacology, JIPMER, Puducherry, India) for guiding us in the laboratory works. We are also grateful to Ms. Abitha Begam Saleem and Ms. Sujatha Rajish (Department of General Medicine, JIPMER, Puducherry, India) who processed the samples for HbA1c estimation.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: We are greatly indebted to the JIPMER, Puducherry, India for having supported the study through the intramural research grants (JIP/Res/Intra-MD/MS/01/2014; JIP/Res/Intra-MD, MS/sec/05/2014).

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/dmpt-2018-0030).

Received: 2018-09-25
Accepted: 2018-10-26
Published Online: 2018-11-15
Published in Print: 2018-12-19

©2018 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Gérard Siest Prize awarded to Alžběta Hlaváčková at the 9th Santorini Conference
  4. Opinion Paper
  5. Personalized medicine into health national services: barriers and potentialities
  6. Case Report
  7. Early disease relapse in a patient with colorectal cancer who harbors genetic variants of DPYD, TYMS, MTHFR and DHFR after treatment with 5-fluorouracil-based chemotherapy
  8. Original Articles
  9. Effect of baseline renal and hepatic function on the incidence of adverse drug events: the Japan Adverse Drug Events study
  10. Lack of effect of the SLC47A1 and SLC47A2 gene polymorphisms on the glycemic response to metformin in type 2 diabetes mellitus patients
  11. Effects of CYP2C19*17 polymorphisms on the efficacy and safety of bromodigyrochlorophenylbenzodiazepine in patients with anxiety disorder and comorbid alcohol use disorder
  12. Pharmacogenetic testing by polymorphic markers G1846A (CYP2D6*4) and C100T (CYP2D6*10) of the CYP2D6 gene in coronary heart disease patients taking ββ-blockers in the Republic of Sakha (YAKUTIA)
  13. Acknowledgment
https://doi.org/10.1515/dmpt-2018-0030
Keywords for this article
metformin; multidrug and toxin extrusion proteins; single nucleotide polymorphism; solute carrier family 47 member 1 (SLC47A1); solute carrier family 47 member 2 (SLC47A2)

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Gérard Siest Prize awarded to Alžběta Hlaváčková at the 9th Santorini Conference
  4. Opinion Paper
  5. Personalized medicine into health national services: barriers and potentialities
  6. Case Report
  7. Early disease relapse in a patient with colorectal cancer who harbors genetic variants of DPYD, TYMS, MTHFR and DHFR after treatment with 5-fluorouracil-based chemotherapy
  8. Original Articles
  9. Effect of baseline renal and hepatic function on the incidence of adverse drug events: the Japan Adverse Drug Events study
  10. Lack of effect of the SLC47A1 and SLC47A2 gene polymorphisms on the glycemic response to metformin in type 2 diabetes mellitus patients
  11. Effects of CYP2C19*17 polymorphisms on the efficacy and safety of bromodigyrochlorophenylbenzodiazepine in patients with anxiety disorder and comorbid alcohol use disorder
  12. Pharmacogenetic testing by polymorphic markers G1846A (CYP2D6*4) and C100T (CYP2D6*10) of the CYP2D6 gene in coronary heart disease patients taking ββ-blockers in the Republic of Sakha (YAKUTIA)
  13. Acknowledgment
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