Pharmacogenetic Evaluation of Metformin and Sulphonylurea Response in Mexican Mestizos with Type 2 Diabetes

Curr Drug Metab. 2020;21(4):291-300. doi: 10.2174/1389200221666200514125443.

Abstract

Background: In Mexico, approximately 25% of patients with type 2 diabetes (T2D) have adequate glycemic control. Polymorphisms in pharmacogenetic genes have been shown to have clinical consequences resulting in drug toxicity or therapeutic inefficacy.

Objective: The study aimed to evaluate the impact of variants in genes known to be involved in response to oral hypoglycemic drugs, such as CYP2C9, OCT, MATE, ABCA1 and C11orf65, in the Mexican Mestizo population of T2D patients.

Methods: In this study, 265 patients with T2D were enrolled from the Hospital Juárez de México, Mexico City. Genotyping was performed by TaqMan® assays. SNP-SNP interactions were analyzed using the multifactor dimensionality reduction (MDR) method.

Results: Carriers of the del allele of rs72552763 could achieve better glycemic control than noncarriers. There was a significant difference in plasma glucose and HbA1c levels among rs622342 genotypes. The results suggested an SNP-SNP interaction between rs72552763 and rs622342 OCT1 and rs12943590 MATE2.

Conclusion: The interaction between rs72552763 and rs622342 in OCT1, and rs12943590 in MATE2 suggested an important role of these polymorphisms in metformin response in T2D Mexican Mestizo population.

Keywords: MATE; Mexican population; OCT; allele frequency; oral hypoglycemic therapy; pharmacogenetics; polymorphism..

MeSH terms

  • ATP Binding Cassette Transporter 1 / metabolism
  • Adult
  • Aged
  • Alleles
  • Cytochrome P-450 CYP2C9 / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genotype
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metformin / therapeutic use*
  • Mexico / epidemiology
  • Middle Aged
  • Octamer Transcription Factor-1 / metabolism
  • Organic Cation Transport Proteins / metabolism
  • Polymorphism, Single Nucleotide

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • Hypoglycemic Agents
  • Octamer Transcription Factor-1
  • Organic Cation Transport Proteins
  • POU2F1 protein, human
  • SLC47A1 protein, human
  • SLC47A2 protein, human
  • Metformin
  • Cytochrome P-450 CYP2C9