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The Effect of CYP2C9 Genotype Variants in Type 2 Diabetes on the Pharmacological Effectiveness of Sulfonylureas, Diabetic Retinopathy, and Nephropathy

AIM: Type 2 diabetes (T2D), as a major cause of morbidity and mortality, is predicted to have a prevalence of 629 million by 2045. As diabetic patients show considerable inter-individual variation in response to antidiabetic treatment, this study aimed to investigate the gene polymorphism of cytochr...

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Autores principales: Saberi, Meisam, Ramazani, Zahra, Rashidi, Homeira, Saberi, Alihossein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308133/
https://www.ncbi.nlm.nih.gov/pubmed/32606720
http://dx.doi.org/10.2147/VHRM.S230639
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author Saberi, Meisam
Ramazani, Zahra
Rashidi, Homeira
Saberi, Alihossein
author_facet Saberi, Meisam
Ramazani, Zahra
Rashidi, Homeira
Saberi, Alihossein
author_sort Saberi, Meisam
collection PubMed
description AIM: Type 2 diabetes (T2D), as a major cause of morbidity and mortality, is predicted to have a prevalence of 629 million by 2045. As diabetic patients show considerable inter-individual variation in response to antidiabetic treatment, this study aimed to investigate the gene polymorphism of cytochrome P450 as well as the effectiveness and safety of glibenclamide and gliclazide for different genotypes of CYP2C9. Besides, the chronic side effects of T2D including retinal microvasculature complications or retinopathy and renal dysfunction due to nephropathy in different genotypes were considered. PATIENTS AND METHODS: The participants including 80 T2D patients treated with glibenclamide or gliclazide were recruited from university hospitals of Ahvaz Jundishpur University of Medical Sciences, Ahvaz, in the southwest of Iran. Blood samples were collected from the patients at 2.5h after the morning dose of glibenclamide and 12h after the last dose of gliclazide. Genotyping from the extracted DNA was, then, performed using PCR-RFLP. The plasma level of glibenclamide and gliclazide was, in turn, measured by the reverse-phase high-pressure liquid chromatography. RESULTS: The results showed that the wild-type allele, i.e., CYP2C9*1, occurred in the highest frequency (0.8), while the frequency rates of the mutant allele, i.e., CYP2C9*2 and CYP2C9*3, were 0.15 and 0.05, respectively. Moreover, no significant association was found between any of the genotypes as well as the clinical and biochemical characteristics of the patients. The findings also showed that the plasma level of sulfonylureas (i.e., glibenclamide and gliclazide) was the highest in the patients with the CYP2C9*3 allele. It was also found that 75.9% of the patients with variant genotypes had experienced hypoglycemia events. Furthermore, in the absence of wild type allele, a significant increase was observed in retinopathy (p=0.039) and nephropathy (p=0.05). CONCLUSION: The findings can provide guidelines for the optimal management of the treatment protocols with sulfonylurea intended to control the T2D complications.
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spelling pubmed-73081332020-06-29 The Effect of CYP2C9 Genotype Variants in Type 2 Diabetes on the Pharmacological Effectiveness of Sulfonylureas, Diabetic Retinopathy, and Nephropathy Saberi, Meisam Ramazani, Zahra Rashidi, Homeira Saberi, Alihossein Vasc Health Risk Manag Original Research AIM: Type 2 diabetes (T2D), as a major cause of morbidity and mortality, is predicted to have a prevalence of 629 million by 2045. As diabetic patients show considerable inter-individual variation in response to antidiabetic treatment, this study aimed to investigate the gene polymorphism of cytochrome P450 as well as the effectiveness and safety of glibenclamide and gliclazide for different genotypes of CYP2C9. Besides, the chronic side effects of T2D including retinal microvasculature complications or retinopathy and renal dysfunction due to nephropathy in different genotypes were considered. PATIENTS AND METHODS: The participants including 80 T2D patients treated with glibenclamide or gliclazide were recruited from university hospitals of Ahvaz Jundishpur University of Medical Sciences, Ahvaz, in the southwest of Iran. Blood samples were collected from the patients at 2.5h after the morning dose of glibenclamide and 12h after the last dose of gliclazide. Genotyping from the extracted DNA was, then, performed using PCR-RFLP. The plasma level of glibenclamide and gliclazide was, in turn, measured by the reverse-phase high-pressure liquid chromatography. RESULTS: The results showed that the wild-type allele, i.e., CYP2C9*1, occurred in the highest frequency (0.8), while the frequency rates of the mutant allele, i.e., CYP2C9*2 and CYP2C9*3, were 0.15 and 0.05, respectively. Moreover, no significant association was found between any of the genotypes as well as the clinical and biochemical characteristics of the patients. The findings also showed that the plasma level of sulfonylureas (i.e., glibenclamide and gliclazide) was the highest in the patients with the CYP2C9*3 allele. It was also found that 75.9% of the patients with variant genotypes had experienced hypoglycemia events. Furthermore, in the absence of wild type allele, a significant increase was observed in retinopathy (p=0.039) and nephropathy (p=0.05). CONCLUSION: The findings can provide guidelines for the optimal management of the treatment protocols with sulfonylurea intended to control the T2D complications. Dove 2020-06-18 /pmc/articles/PMC7308133/ /pubmed/32606720 http://dx.doi.org/10.2147/VHRM.S230639 Text en © 2020 Saberi et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Saberi, Meisam
Ramazani, Zahra
Rashidi, Homeira
Saberi, Alihossein
The Effect of CYP2C9 Genotype Variants in Type 2 Diabetes on the Pharmacological Effectiveness of Sulfonylureas, Diabetic Retinopathy, and Nephropathy
title The Effect of CYP2C9 Genotype Variants in Type 2 Diabetes on the Pharmacological Effectiveness of Sulfonylureas, Diabetic Retinopathy, and Nephropathy
title_full The Effect of CYP2C9 Genotype Variants in Type 2 Diabetes on the Pharmacological Effectiveness of Sulfonylureas, Diabetic Retinopathy, and Nephropathy
title_fullStr The Effect of CYP2C9 Genotype Variants in Type 2 Diabetes on the Pharmacological Effectiveness of Sulfonylureas, Diabetic Retinopathy, and Nephropathy
title_full_unstemmed The Effect of CYP2C9 Genotype Variants in Type 2 Diabetes on the Pharmacological Effectiveness of Sulfonylureas, Diabetic Retinopathy, and Nephropathy
title_short The Effect of CYP2C9 Genotype Variants in Type 2 Diabetes on the Pharmacological Effectiveness of Sulfonylureas, Diabetic Retinopathy, and Nephropathy
title_sort effect of cyp2c9 genotype variants in type 2 diabetes on the pharmacological effectiveness of sulfonylureas, diabetic retinopathy, and nephropathy
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308133/
https://www.ncbi.nlm.nih.gov/pubmed/32606720
http://dx.doi.org/10.2147/VHRM.S230639
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