Pharmacogenetics of Metformin Transporters Suggests No Association with Therapeutic Inefficacy among Diabetes Type 2 Mexican Patients
Mexico has been under official epidemiological alert due to diabetes since 2016. This study presents new information on the frequency and variants of metformin transporters OCT1, OCT2, OCT3, <i>ABCB1</i>, and <i>CYP2C9</i> variants as well. It also reports the association wit...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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MDPI AG,
2022-06-01T00:00:00Z.
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| Summary: | Mexico has been under official epidemiological alert due to diabetes since 2016. This study presents new information on the frequency and variants of metformin transporters OCT1, OCT2, OCT3, <i>ABCB1</i>, and <i>CYP2C9</i> variants as well. It also reports the association with HbA1c control on 103 DMT2 patients. They were genotyped through real-time PCR (TaqMan assays) and grouped according to treatment: metformin and metformin + glibenclamide. Metformin plasmatic levels were determined through mass spectrometry. The analysis of HbA1c showed statistical significance across genotypes in polymorphisms rs72552763 (<i>p</i> = 0.022), rs622342 (<i>p</i> = 0.009), rs1128503 (<i>p</i> = 0.021), and rs2032582 (<i>p</i> = 0.009) within the monotherapy group. Bivariate analysis found no association between any polymorphism and HbA1c control. Two logistic regression models accounted for two diplotypes in OCT1 and <i>ABCB1</i>, including statistically significant covariates. The first model yielded significance in age (<i>p</i> = 0.026), treatment period [<i>p</i> = 0.001], BMI ≥ 25 kg/m<sup>2</sup> (<i>p</i> = 0.043), and combined therapy (<i>p</i> < 0.001). There was no association with <i>GAT/GAT</i> of rs72552763 or <i>A/A</i> rs622342 in OCT1. The second model yielded significance in age (<i>p</i> = 0.017), treatment period (<i>p</i> = 0.001), BMI ≥ 25 kg/m<sup>2</sup> (<i>p</i> = 0.042), and combined therapy (<i>p</i> < 0.001), finding no association with <i>C/C</i> of rs1128503 or <i>G/G</i> of rs2032582 in <i>ABCB1</i>. Our multinomial logistic regression results may benefit future predictive analyses in diabetic populations. |
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| Item Description: | 10.3390/ph15070774 1424-8247 |