期刊
GENE
卷 823, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.gene.2022.146382
关键词
Metformin; Type 2 diabetes mellitus; HbA1c; SLC22A3
资金
- Research Department of the School of Medicine-Shahid Beheshti University of Medical Sci-ences [23764]
This study investigated the association of rs543159 and rs1317652 variants in the SLC22A3 gene with response to metformin monotherapy in newly diagnosed patients with T2DM. The results suggest that these genetic variations may be correlated with variability in treatment response.
Background and aims: Among anti-diabetic medications, metformin has been proven to be the preferred initial pharmacologic agent for type 2 diabetes mellitus (T2DM) treatment. Despite its safety and efficacy, the response to metformin varies between individuals. Genetic variations, especially within genes involved in pharmacoki-netics and pharmacodynamics of metformin (e.g SLC22A3), have been suggested to be responsible for the observed inter-individual differences. By considering the undeniable role of organic cation transporter 3 in he-patic uptake of metformin, this study was aimed to investigate the association of rs543159 and rs1317652 variants in SLC22A3 gene with response to metformin monotherapy in newly diagnosed patients with T2DM.& nbsp;Methods: The study included 200 T2DM patients who received metformin monotherapy for 25 weeks. The pa-tients were classified into 2 groups according to their HbA1c values: the responders (reduction in HbA1c levels by at least 1% after 25 weeks treatment with metformin) and non-responders (less than 1% reduction in HbA1c levels after 25 weeks treatment with metformin). We used tetra ARMS-PCR method to determine genotypes of the target variants. Results: For the rs543159, CA and AA genotypes were more frequent in responders as compared to non-responders (OR = 2.48; 95% CI = 1.28-4.78, P-value = 0.0057) under the dominant model. In case of rs1317652 CC and CT genotypes were more frequent in metformin responders as compared to non-responder group (OR = 2.49; 95% CI = 1.32-4.70, P-value = 0.0043) under the dominant model. Parameters such as fasting blood sugar (FBS), HbA1c, and total cholesterol (TC) levels were significantly lower in the responder group after 25 weeks of metformin monotherapy. Moreover, according to the result of multiple linear regression rs543159 and base line HbA1c values are significantly associated with response to metformin monotherapy. Conclusion: Our results suggested that rs543159 and rs1317652 in SLC22A3 gene might be associated with variability in response to metformin therapy in T2DM patients.
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