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Effects and interaction of single nucleotide polymorphisms at the pharmacokinetic/pharmacodynamic site: insights from the Rotterdam study into metformin clinical response and dose titration.
- Source :
-
The pharmacogenomics journal [Pharmacogenomics J] 2024 Oct 07; Vol. 24 (6), pp. 31. Date of Electronic Publication: 2024 Oct 07. - Publication Year :
- 2024
-
Abstract
- Our study investigated the impact of genetic variations on metformin glycemic response in a cohort from the Rotterdam Study, comprising 14,926 individuals followed for up to 27 years. Among 1285 metformin users of European ancestry, using linear mixed models, we analyzed the association of single nucleotide polymorphisms (SNPs) and a Polygenic Risk Score (PRS) with glycemic response, measured by changes in metformin dosage or HbA1c levels. While individual genetic variants showed no significant association, rs622342 on SLC2A1 correlated with increased glycemic response only in metformin monotherapy patients (β = -2.09, P-value < 0.001). The collective effect of variants, as represented by PRS, weakly correlated with changes in metformin dosage (β = 0.023, P-value = 0.027). Synergistic interaction was observed between rs7124355 and rs8192675. Our findings suggest that while higher PRS correlates with increased metformin dosage, its modest effect size limits clinical utility, emphasizing the need for future research in diverse populations to refine genetic risk models.<br /> (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Subjects :
- Aged
Female
Humans
Male
Middle Aged
Blood Glucose analysis
Dose-Response Relationship, Drug
Glycated Hemoglobin analysis
Netherlands
White People genetics
Diabetes Mellitus, Type 2 drug therapy
Diabetes Mellitus, Type 2 genetics
Hypoglycemic Agents pharmacokinetics
Hypoglycemic Agents therapeutic use
Metformin pharmacokinetics
Metformin therapeutic use
Polymorphism, Single Nucleotide
Subjects
Details
- Language :
- English
- ISSN :
- 1473-1150
- Volume :
- 24
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The pharmacogenomics journal
- Publication Type :
- Academic Journal
- Accession number :
- 39375343
- Full Text :
- https://doi.org/10.1038/s41397-024-00352-z