Pharmacogenomics of Sulfonylureas Response in Relation to rs7754840 Polymorphisms in Cyclin-Dependent Kinase 5 Regulatory Subunit-associated Protein 1-like (CDKAL1) Gene in Iranian Type 2 Diabetes Patients
Background: Sulfonylureas are important drugs of choice for treatment of type 2 diabetes mellitus (T2DM). It is suggested that differential response to sulfonylureas from T2DM patients is under influence of single nucleotide polymorphisms in some of the target genes. In spite of favorable therapeuti...
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| Format: | Article |
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Wolters Kluwer Medknow Publications
2018-01-01
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| Series: | Advanced Biomedical Research |
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| Online Access: | http://www.advbiores.net/article.asp?issn=2277-9175;year=2018;volume=7;issue=1;spage=96;epage=96;aulast=Soltani |
| _version_ | 1818134309480955904 |
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| author | Goljahan Soltani Zahra Hatefi Ahmad Reza Salehi Sharifeh Khosravi Moosa Rahimi Ghiasi Keimer Teke Ashraf Aminorroaya Rasoul Salehi |
| author_facet | Goljahan Soltani Zahra Hatefi Ahmad Reza Salehi Sharifeh Khosravi Moosa Rahimi Ghiasi Keimer Teke Ashraf Aminorroaya Rasoul Salehi |
| author_sort | Goljahan Soltani |
| collection | DOAJ |
| description | Background: Sulfonylureas are important drugs of choice for treatment of type 2 diabetes mellitus (T2DM). It is suggested that differential response to sulfonylureas from T2DM patients is under influence of single nucleotide polymorphisms in some of the target genes. In spite of favorable therapeutic effects, sulfonylureas are associated with some adverse side effects such as microvascular complications and stroke, especially in older patients. Therefore, for T2DM patients who are getting less benefit, sulfonylureas should be avoided. Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like (CDKAL1) gene variation is reported to be associated with sulfonylureas effectiveness. Due to the inconsistency of available data regarding association of rs7754840 in CDKAL1 gene with sulfonylureas response in T2DM patients, the present study is conducted. Materials and Methods: Fifty-one diabetic patients sensitive to sulfonylureas and 51 patients resistant to sulfonylureas treatment were recruited to this study. After extraction of DNA from patients' peripheral blood samples, rs7754840 single-nucleotide polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism assay using MaeII (Tail) restriction enzyme. Results: Frequency of G allele in resistant group was more than sensitive group (71, 6% vs. 57, 8%). Regression analysis was shown significant association between GG genotype and higher risk of resistance to sulfonylureas treatment (odds ratio = 2.250 [95% confidential intervals: 1.010–5.012]; P = 0.046). Conclusion: Our data confirmed that genotypes of rs7754840 are significantly associated with sulfonylureas treatment response. rs7754840 in CDKAL1 gene in combination with other clinicopathological findings would help to move towards personalized therapy of T2DM patients. |
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| institution | Directory Open Access Journal |
| issn | 2277-9175 |
| language | English |
| last_indexed | 2024-12-11T09:06:34Z |
| publishDate | 2018-01-01 |
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| series | Advanced Biomedical Research |
| spelling | doaj.art-3730e506e2e844fcb7831b306e7aeb8d2022-12-22T01:13:37ZengWolters Kluwer Medknow PublicationsAdvanced Biomedical Research2277-91752018-01-0171969610.4103/abr.abr_144_17Pharmacogenomics of Sulfonylureas Response in Relation to rs7754840 Polymorphisms in Cyclin-Dependent Kinase 5 Regulatory Subunit-associated Protein 1-like (CDKAL1) Gene in Iranian Type 2 Diabetes PatientsGoljahan SoltaniZahra HatefiAhmad Reza SalehiSharifeh KhosraviMoosa Rahimi GhiasiKeimer TekeAshraf AminorroayaRasoul SalehiBackground: Sulfonylureas are important drugs of choice for treatment of type 2 diabetes mellitus (T2DM). It is suggested that differential response to sulfonylureas from T2DM patients is under influence of single nucleotide polymorphisms in some of the target genes. In spite of favorable therapeutic effects, sulfonylureas are associated with some adverse side effects such as microvascular complications and stroke, especially in older patients. Therefore, for T2DM patients who are getting less benefit, sulfonylureas should be avoided. Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like (CDKAL1) gene variation is reported to be associated with sulfonylureas effectiveness. Due to the inconsistency of available data regarding association of rs7754840 in CDKAL1 gene with sulfonylureas response in T2DM patients, the present study is conducted. Materials and Methods: Fifty-one diabetic patients sensitive to sulfonylureas and 51 patients resistant to sulfonylureas treatment were recruited to this study. After extraction of DNA from patients' peripheral blood samples, rs7754840 single-nucleotide polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism assay using MaeII (Tail) restriction enzyme. Results: Frequency of G allele in resistant group was more than sensitive group (71, 6% vs. 57, 8%). Regression analysis was shown significant association between GG genotype and higher risk of resistance to sulfonylureas treatment (odds ratio = 2.250 [95% confidential intervals: 1.010–5.012]; P = 0.046). Conclusion: Our data confirmed that genotypes of rs7754840 are significantly associated with sulfonylureas treatment response. rs7754840 in CDKAL1 gene in combination with other clinicopathological findings would help to move towards personalized therapy of T2DM patients.http://www.advbiores.net/article.asp?issn=2277-9175;year=2018;volume=7;issue=1;spage=96;epage=96;aulast=SoltaniCyclin-dependent kinase 5 regulatory subunit-associated protein 1-likeglycemic controlsingle nucleotide polymorphismsulfonylureastype 2 diabetes |
| spellingShingle | Goljahan Soltani Zahra Hatefi Ahmad Reza Salehi Sharifeh Khosravi Moosa Rahimi Ghiasi Keimer Teke Ashraf Aminorroaya Rasoul Salehi Pharmacogenomics of Sulfonylureas Response in Relation to rs7754840 Polymorphisms in Cyclin-Dependent Kinase 5 Regulatory Subunit-associated Protein 1-like (CDKAL1) Gene in Iranian Type 2 Diabetes Patients Advanced Biomedical Research Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like glycemic control single nucleotide polymorphism sulfonylureas type 2 diabetes |
| title | Pharmacogenomics of Sulfonylureas Response in Relation to rs7754840 Polymorphisms in Cyclin-Dependent Kinase 5 Regulatory Subunit-associated Protein 1-like (CDKAL1) Gene in Iranian Type 2 Diabetes Patients |
| title_full | Pharmacogenomics of Sulfonylureas Response in Relation to rs7754840 Polymorphisms in Cyclin-Dependent Kinase 5 Regulatory Subunit-associated Protein 1-like (CDKAL1) Gene in Iranian Type 2 Diabetes Patients |
| title_fullStr | Pharmacogenomics of Sulfonylureas Response in Relation to rs7754840 Polymorphisms in Cyclin-Dependent Kinase 5 Regulatory Subunit-associated Protein 1-like (CDKAL1) Gene in Iranian Type 2 Diabetes Patients |
| title_full_unstemmed | Pharmacogenomics of Sulfonylureas Response in Relation to rs7754840 Polymorphisms in Cyclin-Dependent Kinase 5 Regulatory Subunit-associated Protein 1-like (CDKAL1) Gene in Iranian Type 2 Diabetes Patients |
| title_short | Pharmacogenomics of Sulfonylureas Response in Relation to rs7754840 Polymorphisms in Cyclin-Dependent Kinase 5 Regulatory Subunit-associated Protein 1-like (CDKAL1) Gene in Iranian Type 2 Diabetes Patients |
| title_sort | pharmacogenomics of sulfonylureas response in relation to rs7754840 polymorphisms in cyclin dependent kinase 5 regulatory subunit associated protein 1 like cdkal1 gene in iranian type 2 diabetes patients |
| topic | Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like glycemic control single nucleotide polymorphism sulfonylureas type 2 diabetes |
| url | http://www.advbiores.net/article.asp?issn=2277-9175;year=2018;volume=7;issue=1;spage=96;epage=96;aulast=Soltani |
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