Transporters, TBC1D4, and ARID5B Variants to Explain Glycated Hemoglobin Variability in Patients with Type 2 Diabetes.
Pharmacology
; 106(11-12): 588-596, 2021.
Article
in En
| MEDLINE
| ID: mdl-34265779
ABSTRACT
INTRODUCTION:
Genetic variants could aid in predicting antidiabetic drug response by associating them with markers of glucose control, such as glycated hemoglobin (HbA1c). However, pharmacogenetic implementation for antidiabetics is still under development, as the list of actionable markers is being populated and validated. This study explores potential associations between genetic variants and plasma levels of HbA1c in 100 patients under treatment with metformin.METHODS:
HbA1c was measured in a clinical chemistry analyzer (Roche), genotyping was performed in an Illumina-GSA array and data were analyzed using PLINK. Association and prediction models were developed using R and a 10-fold cross-validation approach.RESULTS:
We identified genetic variants on SLC47A1, SLC28A1, ABCG2, TBC1D4, and ARID5B that can explain up to 55% of the interindividual variability of HbA1c plasma levels in diabetic patients under treatment. Variants on SLC47A1, SLC28A1, and ABCG2 likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis.CONCLUSIONS:
Our results confirm previous genetic associations and point to previously unassociated gene variants for metformin PK and glucose control.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Glycated Hemoglobin
/
GTPase-Activating Proteins
/
Diabetes Mellitus, Type 2
/
DNA-Binding Proteins
/
Hypoglycemic Agents
/
Metformin
Type of study:
Prognostic_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Pharmacology
Year:
2021
Document type:
Article
Affiliation country:
Mexico