Pharmacogenetics: Influence of CYP2C9*2 and *3 alleles polymorphisms on Iraqi type 2 diabetic patients
Abstract Background: Sulfonylureas (SUs) are the most prescribed anti-diabetic drugs. The enzyme responsible for metabolizing of SUs is hepatic cytochrome P4502C9 (CYP2C9). The CYP2C9 gene has numerous allelic variations; among those, the CYP2C9*2 and CYP2C9*3 are the most common and clinically sign...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2024-01-01
|
| Series: | Medical Journal of Babylon |
| Subjects: | |
| Online Access: | https://doi.org/10.4103/MJBL.MJBL_382_23 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832586523354071040 |
|---|---|
| author | Ghada S. Rasool Asmaa A. Hussien Suhad R. Al-Tayie Salwa J. Al-Awadi Hussein OM Al-Dahmoshi |
| author_facet | Ghada S. Rasool Asmaa A. Hussien Suhad R. Al-Tayie Salwa J. Al-Awadi Hussein OM Al-Dahmoshi |
| author_sort | Ghada S. Rasool |
| collection | DOAJ |
| description | Abstract Background: Sulfonylureas (SUs) are the most prescribed anti-diabetic drugs. The enzyme responsible for metabolizing of SUs is hepatic cytochrome P4502C9 (CYP2C9). The CYP2C9 gene has numerous allelic variations; among those, the CYP2C9*2 and CYP2C9*3 are the most common and clinically significant allelic variations. The pharmacokinetics of SUs are dramatically impacted by CYP2C9 genotype. Objective: Evaluation of the association of genetic polymorphisms in CYP2C9 gene with the efficacy of glibenclamide (GB), second-generation SUs, by investigating two CYP2C9 allelic variants. Materials and Methods: Blood samples were collected from 113 type 2 diabetes patients. Allele specific amplification-polymerase chain reaction was used to genotype the CYP2C9 gene. Fasting serum glucose, fasting insulin, and glycated hemoglobin (HbA1c) levels were measured as part of the biochemical analysis. Results: The CYP2C9 gene variants were analyzed in a study group. The results exposed that 75 patients carried the wild (CYP2C9*1/*1) genotype, 25 were heterozygote allele (CYP2C9*1/*2) for CYP2C9*2 gene, 4 were homozygous for the variant CYP2C9*2 allele (CYP2C9*2/*2), and 9 were heterozygous for the variant CYP2C9*3 allele (CYP2C9*1/*3). Statistically significant difference was found in mean HbA1c between the mutant and wild alleles group (P = 0.044). The mean HbA1c for those carrying the CYP2C9*2 and*3 alleles (n = 38) was 8.4750 compared to 9.3177 for those carrying the CYP2C9*1 allele (n = 75), which indicate better glycemic control. Conclusion: The accordance of CYP2C9*2 and*3 was found to be associated with severe hypoglycemia (odd ratio [OR] = 2.045). The OR suggests a strong association between CYP2C9*2 and*3 alleles and hypoglycemia. Our findings imply that the diabetic patients with CYP2C9 polymorphism are more likely to suffer hypoglycemia than those with wild type alleles when treated with GB. |
| format | Article |
| id | doaj-art-99b38f8980e547c0b94b04d5925d90bd |
| institution | Kabale University |
| issn | 1812-156X 2312-6760 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Medical Journal of Babylon |
| spelling | doaj-art-99b38f8980e547c0b94b04d5925d90bd2025-01-25T10:14:50ZengWolters Kluwer Medknow PublicationsMedical Journal of Babylon1812-156X2312-67602024-01-0121111812310.4103/MJBL.MJBL_382_23Pharmacogenetics: Influence of CYP2C9*2 and *3 alleles polymorphisms on Iraqi type 2 diabetic patientsGhada S. RasoolAsmaa A. HussienSuhad R. Al-TayieSalwa J. Al-AwadiHussein OM Al-DahmoshiAbstract Background: Sulfonylureas (SUs) are the most prescribed anti-diabetic drugs. The enzyme responsible for metabolizing of SUs is hepatic cytochrome P4502C9 (CYP2C9). The CYP2C9 gene has numerous allelic variations; among those, the CYP2C9*2 and CYP2C9*3 are the most common and clinically significant allelic variations. The pharmacokinetics of SUs are dramatically impacted by CYP2C9 genotype. Objective: Evaluation of the association of genetic polymorphisms in CYP2C9 gene with the efficacy of glibenclamide (GB), second-generation SUs, by investigating two CYP2C9 allelic variants. Materials and Methods: Blood samples were collected from 113 type 2 diabetes patients. Allele specific amplification-polymerase chain reaction was used to genotype the CYP2C9 gene. Fasting serum glucose, fasting insulin, and glycated hemoglobin (HbA1c) levels were measured as part of the biochemical analysis. Results: The CYP2C9 gene variants were analyzed in a study group. The results exposed that 75 patients carried the wild (CYP2C9*1/*1) genotype, 25 were heterozygote allele (CYP2C9*1/*2) for CYP2C9*2 gene, 4 were homozygous for the variant CYP2C9*2 allele (CYP2C9*2/*2), and 9 were heterozygous for the variant CYP2C9*3 allele (CYP2C9*1/*3). Statistically significant difference was found in mean HbA1c between the mutant and wild alleles group (P = 0.044). The mean HbA1c for those carrying the CYP2C9*2 and*3 alleles (n = 38) was 8.4750 compared to 9.3177 for those carrying the CYP2C9*1 allele (n = 75), which indicate better glycemic control. Conclusion: The accordance of CYP2C9*2 and*3 was found to be associated with severe hypoglycemia (odd ratio [OR] = 2.045). The OR suggests a strong association between CYP2C9*2 and*3 alleles and hypoglycemia. Our findings imply that the diabetic patients with CYP2C9 polymorphism are more likely to suffer hypoglycemia than those with wild type alleles when treated with GB.https://doi.org/10.4103/MJBL.MJBL_382_23cyp2c9diabetes mellitus type 2glibenclamidepharmacogeneticsulphonylurea |
| spellingShingle | Ghada S. Rasool Asmaa A. Hussien Suhad R. Al-Tayie Salwa J. Al-Awadi Hussein OM Al-Dahmoshi Pharmacogenetics: Influence of CYP2C9*2 and *3 alleles polymorphisms on Iraqi type 2 diabetic patients Medical Journal of Babylon cyp2c9 diabetes mellitus type 2 glibenclamide pharmacogenetic sulphonylurea |
| title | Pharmacogenetics: Influence of CYP2C9*2 and *3 alleles polymorphisms on Iraqi type 2 diabetic patients |
| title_full | Pharmacogenetics: Influence of CYP2C9*2 and *3 alleles polymorphisms on Iraqi type 2 diabetic patients |
| title_fullStr | Pharmacogenetics: Influence of CYP2C9*2 and *3 alleles polymorphisms on Iraqi type 2 diabetic patients |
| title_full_unstemmed | Pharmacogenetics: Influence of CYP2C9*2 and *3 alleles polymorphisms on Iraqi type 2 diabetic patients |
| title_short | Pharmacogenetics: Influence of CYP2C9*2 and *3 alleles polymorphisms on Iraqi type 2 diabetic patients |
| title_sort | pharmacogenetics influence of cyp2c9 2 and 3 alleles polymorphisms on iraqi type 2 diabetic patients |
| topic | cyp2c9 diabetes mellitus type 2 glibenclamide pharmacogenetic sulphonylurea |
| url | https://doi.org/10.4103/MJBL.MJBL_382_23 |
| work_keys_str_mv | AT ghadasrasool pharmacogeneticsinfluenceofcyp2c92and3allelespolymorphismsoniraqitype2diabeticpatients AT asmaaahussien pharmacogeneticsinfluenceofcyp2c92and3allelespolymorphismsoniraqitype2diabeticpatients AT suhadraltayie pharmacogeneticsinfluenceofcyp2c92and3allelespolymorphismsoniraqitype2diabeticpatients AT salwajalawadi pharmacogeneticsinfluenceofcyp2c92and3allelespolymorphismsoniraqitype2diabeticpatients AT husseinomaldahmoshi pharmacogeneticsinfluenceofcyp2c92and3allelespolymorphismsoniraqitype2diabeticpatients |