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Published in: Journal of Diabetes & Metabolic Disorders 2/2021

01-12-2021 | Sulfonylurea | Research article

A pharmacogenetic pilot study of CYP2C9 common genetic variant and sulfonylureas therapeutic response in type 2 diabetes mellitus patients

Authors: Elham Didari, Negar Sarhangi, Mahdi Afshari, Hamid Reza Aghaei Meybodi, Mandana Hasanzad

Published in: Journal of Diabetes & Metabolic Disorders | Issue 2/2021

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Abstract

Background

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is associated with elevated blood glucose levels. Sulfonylureas (SFUs) are the most widely used among the oral antidiabetic drugs that are highly metabolized by cytochrome P450 family 2 subfamily C member 9 (CYP2C9). The CYP2C9 has been shown to be associated with a better glycemic response to SFUs and a lower treatment failure rate. The aim of the present study was to assess the influence of the CYP2C9 rs1067910 gene variant on the SFUs response in a group of Iranian patients for the first time.

Methods

Blood samples were taken from 30 patients with T2DM under sulfonylurea treatment. DNA extraction was performed using Salting out method, and then genotyping was performed by polymerase chain reaction (PCR) followed by Sanger sequencing.

Results

There was no significant difference in the fasting blood sugar (FBS) between T2DM patients with different genotypes before and after the treatment with SFUs (P = 0.073 and P = 0.893, respectively). Although HbA1c was significantly different among AA, CA and CC carriers before (P = 0.001) and after (P = 0.018) treatment, no significant change was observed after treatment in all three groups.

Conclusions

In the present study based on only 30 samples in pilot survey, it is shown that the therapeutic response to SFUs was not related to rs1057910 CYP2C9 variant.
Literature
1.
go back to reference Stančáková A, Laakso M. Genetics of type 2 diabetes. Novelties in Diabetes. 2016;31:203–20.CrossRef Stančáková A, Laakso M. Genetics of type 2 diabetes. Novelties in Diabetes. 2016;31:203–20.CrossRef
2.
go back to reference Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843.
3.
go back to reference Ogurtsova K, da Rocha FJ, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40–50.CrossRef Ogurtsova K, da Rocha FJ, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40–50.CrossRef
5.
go back to reference Association AD. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013;36(Suppl 1):S67.CrossRef Association AD. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013;36(Suppl 1):S67.CrossRef
6.
go back to reference Mannino GC, Andreozzi F, Sesti G. Pharmacogenetics of type 2 diabetes mellitus, the route toward tailored medicine. Diabetes Metab Res Rev. 2019;35(3):e3109. Mannino GC, Andreozzi F, Sesti G. Pharmacogenetics of type 2 diabetes mellitus, the route toward tailored medicine. Diabetes Metab Res Rev. 2019;35(3):e3109.
7.
go back to reference Belle DJ, Singh H. Genetic factors in drug metabolism. Am Fam Physician. 2008;77(11):1553–60.PubMed Belle DJ, Singh H. Genetic factors in drug metabolism. Am Fam Physician. 2008;77(11):1553–60.PubMed
8.
go back to reference Dujic T. Pharmacogenetics of new classes of antidiabetic drugs. Bosn J Basic Med Sci. 2021. Dujic T. Pharmacogenetics of new classes of antidiabetic drugs. Bosn J Basic Med Sci. 2021.
9.
go back to reference Lee HH, Ho RH. Interindividual and interethnic variability in drug disposition: polymorphisms in organic anion transporting polypeptide 1B1 (OATP1B1; SLCO1B1). Br J Clin Pharmacol. 2017;83(6):1176–84.CrossRef Lee HH, Ho RH. Interindividual and interethnic variability in drug disposition: polymorphisms in organic anion transporting polypeptide 1B1 (OATP1B1; SLCO1B1). Br J Clin Pharmacol. 2017;83(6):1176–84.CrossRef
10.
go back to reference Loganadan N, Huri H, Vethakkan S, Hussein Z. Genetic markers predicting sulphonylurea treatment outcomes in type 2 diabetes patients: current evidence and challenges for clinical implementation. Pharmacogenomics J. 2016;16(3):209–19.CrossRef Loganadan N, Huri H, Vethakkan S, Hussein Z. Genetic markers predicting sulphonylurea treatment outcomes in type 2 diabetes patients: current evidence and challenges for clinical implementation. Pharmacogenomics J. 2016;16(3):209–19.CrossRef
11.
go back to reference Zhang H, Liu X, Kuang H, Yi R, Xing H. Association of sulfonylurea receptor 1 genotype with therapeutic response to gliclazide in type 2 diabetes. Diabetes Res Clin Pract. 2007;77(1):58–61.CrossRef Zhang H, Liu X, Kuang H, Yi R, Xing H. Association of sulfonylurea receptor 1 genotype with therapeutic response to gliclazide in type 2 diabetes. Diabetes Res Clin Pract. 2007;77(1):58–61.CrossRef
12.
go back to reference Udler MS, Kim J, von Grotthuss M, Bonàs-Guarch S, Cole JB, Chiou J, et al. Type 2 diabetes genetic loci informed by multi-trait associations point to disease mechanisms and subtypes: a soft clustering analysis. PLoS Med. 2018;15(9):e1002654. Udler MS, Kim J, von Grotthuss M, Bonàs-Guarch S, Cole JB, Chiou J, et al. Type 2 diabetes genetic loci informed by multi-trait associations point to disease mechanisms and subtypes: a soft clustering analysis. PLoS Med. 2018;15(9):e1002654.
13.
go back to reference Ferder N, Eby CS, Deych E, Harris JK, Ridker PM, Milligan P, et al. Ability of VKORC1 and CYP2C9 to predict therapeutic warfarin dose during the initial weeks of therapy. J Thromb Haemost. 2010;8(1):95–100.CrossRef Ferder N, Eby CS, Deych E, Harris JK, Ridker PM, Milligan P, et al. Ability of VKORC1 and CYP2C9 to predict therapeutic warfarin dose during the initial weeks of therapy. J Thromb Haemost. 2010;8(1):95–100.CrossRef
14.
go back to reference Rettie AE, Jones JP. Clinical and toxicological relevance of CYP2C9: drug-drug interactions and pharmacogenetics. Annu Rev Pharmacol Toxicol. 2005;45:477–94.CrossRef Rettie AE, Jones JP. Clinical and toxicological relevance of CYP2C9: drug-drug interactions and pharmacogenetics. Annu Rev Pharmacol Toxicol. 2005;45:477–94.CrossRef
15.
go back to reference Dujic T, Zhou K, Donnelly LA, Leese G, Palmer CN, Pearson ER. Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea-induced hypoglycaemia: A GoDARTS S tudy. Diabetes Obes Metab. 2018;20(1):211–4.CrossRef Dujic T, Zhou K, Donnelly LA, Leese G, Palmer CN, Pearson ER. Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea-induced hypoglycaemia: A GoDARTS S tudy. Diabetes Obes Metab. 2018;20(1):211–4.CrossRef
16.
go back to reference Holstein A, Plaschke A, Ptak M, Egberts EH, El-Din J, Brockmöller J, et al. Association between CYP2C9 slow metabolizer genotypes and severe hypoglycaemia on medication with sulphonylurea hypoglycaemic agents. Br J Clin Pharmacol. 2005;60(1):103–6.CrossRef Holstein A, Plaschke A, Ptak M, Egberts EH, El-Din J, Brockmöller J, et al. Association between CYP2C9 slow metabolizer genotypes and severe hypoglycaemia on medication with sulphonylurea hypoglycaemic agents. Br J Clin Pharmacol. 2005;60(1):103–6.CrossRef
17.
go back to reference American Diabetes Association (ADA). 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2019. Diabetes Care. 2019;42(Supplement 1):S13-S28. American Diabetes Association (ADA). 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2019. Diabetes Care. 2019;42(Supplement 1):S13-S28.
18.
go back to reference Swen JJ, Wessels JA, Krabben A, Assendelft WJ, Guchelaar HJ. Effect of CYP2C9 polymorphisms on prescribed dose and time-to-stable dose of sulfonylureas in primary care patients with Type 2 diabetes mellitus. Pharmacogenomics. 2010;11(11):1517–23.CrossRef Swen JJ, Wessels JA, Krabben A, Assendelft WJ, Guchelaar HJ. Effect of CYP2C9 polymorphisms on prescribed dose and time-to-stable dose of sulfonylureas in primary care patients with Type 2 diabetes mellitus. Pharmacogenomics. 2010;11(11):1517–23.CrossRef
19.
go back to reference Gökalp O, Gunes A, Çam H, Cure E, AydIn O, Tamer MN, et al. Mild hypoglycaemic attacks induced by sulphonylureas related to CYP2C9, CYP2C19 and CYP2C8 polymorphisms in routine clinical setting. European Eur J Clin Pharmacol. 2011;67(12):1223–9.CrossRef Gökalp O, Gunes A, Çam H, Cure E, AydIn O, Tamer MN, et al. Mild hypoglycaemic attacks induced by sulphonylureas related to CYP2C9, CYP2C19 and CYP2C8 polymorphisms in routine clinical setting. European Eur J Clin Pharmacol. 2011;67(12):1223–9.CrossRef
20.
go back to reference Castelán-Martínez O, Hoyo-Vadillo C, Bazán-Soto T, Cruz M, Tesoro-Cruz E, Valladares-Salgado A. CYP2C9* 3 gene variant contributes independently to glycaemic control in patients with type 2 diabetes treated with glibenclamide. J Clin Pharm Ther. 2018;43(6):768–74.CrossRef Castelán-Martínez O, Hoyo-Vadillo C, Bazán-Soto T, Cruz M, Tesoro-Cruz E, Valladares-Salgado A. CYP2C9* 3 gene variant contributes independently to glycaemic control in patients with type 2 diabetes treated with glibenclamide. J Clin Pharm Ther. 2018;43(6):768–74.CrossRef
21.
go back to reference Naja K, Salami A, El Shamieh S, Fakhoury R. rs622342 in SLC22A1, CYP2C9* 2 and CYP2C9* 3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study. J Pers Med. 2020;10(2):53.CrossRef Naja K, Salami A, El Shamieh S, Fakhoury R. rs622342 in SLC22A1, CYP2C9* 2 and CYP2C9* 3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study. J Pers Med. 2020;10(2):53.CrossRef
22.
go back to reference Zeng W, Guo Y, Chen P, Liu Z, Chen D, Han C. CYP2C93 variant is associated with antidiabetes efficacy of gliclazide in Chinese type 2 diabetes patients. J Diabetes Investig. 2016;7(5):764–8.CrossRef Zeng W, Guo Y, Chen P, Liu Z, Chen D, Han C. CYP2C93 variant is associated with antidiabetes efficacy of gliclazide in Chinese type 2 diabetes patients. J Diabetes Investig. 2016;7(5):764–8.CrossRef
23.
go back to reference Yee J, Heo Y, Kim H, Yoon HY, Song G, Gwak HS. Association Between the CYP2C9 Genotype and Hypoglycemia Among Patients With Type 2 Diabetes Receiving Sulfonylurea Treatment: A Meta-analysis. Clin Ther. 2021; S0149–2918(21)00120-X . Yee J, Heo Y, Kim H, Yoon HY, Song G, Gwak HS. Association Between the CYP2C9 Genotype and Hypoglycemia Among Patients With Type 2 Diabetes Receiving Sulfonylurea Treatment: A Meta-analysis. Clin Ther. 2021; S0149–2918(21)00120-X .
24.
go back to reference Klen J, Dolzan V, Janez A. CYP2C9, KCNJ11 and ABCC8 polymorphisms and the response to sulphonylurea treatment in type 2 diabetes patients. Eur J Clin Pharmacol. 2014;70(4):421–8.CrossRef Klen J, Dolzan V, Janez A. CYP2C9, KCNJ11 and ABCC8 polymorphisms and the response to sulphonylurea treatment in type 2 diabetes patients. Eur J Clin Pharmacol. 2014;70(4):421–8.CrossRef
25.
go back to reference Chen L, Li J, Kaur V, Muhammad A, Fernandez M, Hudson M, et al. The presence of two reduced function variants in CYP2C9 influences the acute response to glipizide. Diabetic Med. 2020;37(12):2124–30.CrossRef Chen L, Li J, Kaur V, Muhammad A, Fernandez M, Hudson M, et al. The presence of two reduced function variants in CYP2C9 influences the acute response to glipizide. Diabetic Med. 2020;37(12):2124–30.CrossRef
Metadata
Title
A pharmacogenetic pilot study of CYP2C9 common genetic variant and sulfonylureas therapeutic response in type 2 diabetes mellitus patients
Authors
Elham Didari
Negar Sarhangi
Mahdi Afshari
Hamid Reza Aghaei Meybodi
Mandana Hasanzad
Publication date
01-12-2021
Publisher
Springer International Publishing
Published in
Journal of Diabetes & Metabolic Disorders / Issue 2/2021
Electronic ISSN: 2251-6581
DOI
https://doi.org/10.1007/s40200-021-00894-0

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