Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide
Previous studies showed associations between variants in TCF7L2 gene and the therapeutic response to sulfonylureas. All sulfonylureas stimulate insulin secretion by the closure of ATP-sensitive potassium (KATP) channel. The aim of the present study was to compare TCF7L2 genotype specific effect of g...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2013/374858 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832564514034286592 |
|---|---|
| author | Martin Javorský Eva Babjaková Lucia Klimčáková Zbynek Schroner Jozef Židzik Mária Štolfová Ján Šalagovič Ivan Tkáč |
| author_facet | Martin Javorský Eva Babjaková Lucia Klimčáková Zbynek Schroner Jozef Židzik Mária Štolfová Ján Šalagovič Ivan Tkáč |
| author_sort | Martin Javorský |
| collection | DOAJ |
| description | Previous studies showed associations between variants in TCF7L2 gene and the therapeutic response to sulfonylureas. All sulfonylureas stimulate insulin secretion by the closure of ATP-sensitive potassium (KATP) channel. The aim of the present study was to compare TCF7L2 genotype specific effect of gliclazide binding to KATP channel A-site (Group 1) with sulfonylureas binding to AB-site (Group 2). A total of 101 patients were treated with sulfonylureas for 6 months as an add-on therapy to the previous metformin treatment. TCF7L2 rs7903146 C/T genotype was identified by real-time PCR with subsequent melting curve analysis. Analyses using the dominant genetic model showed significantly higher effect of gliclazide in the CC genotype group in comparison with combined CT + TT genotype group (1.32±0.15% versus 0.73±0.11%, Padj=0.005). No significant difference in ΔHbA1c between the patients with CC genotype and the T-allele carriers was observed in Group 2. In the multivariate analysis, only the TCF7L2 genotype (P=0.006) and the baseline HbA1c (P<0.001) were significant predictors of ΔHbA1c. After introducing an interaction term between the TCF7L2 genotype and the sulfonylurea type into multivariate model, the interaction became a significant predictor (P=0.023) of ΔHbA1c. The results indicate significantly higher difference in ΔHbA1c among the TCF7L2 genotypes in patients treated with gliclazide than in patients treated with glimepiride, glibenclamide, or glipizide. |
| format | Article |
| id | doaj-art-f8ee17fde8c147c5a382f6cfbc3731b5 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-f8ee17fde8c147c5a382f6cfbc3731b52025-02-03T01:10:59ZengWileyInternational Journal of Endocrinology1687-83371687-83452013-01-01201310.1155/2013/374858374858Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with GliclazideMartin Javorský0Eva Babjaková1Lucia Klimčáková2Zbynek Schroner3Jozef Židzik4Mária Štolfová5Ján Šalagovič6Ivan Tkáč7Department of Internal Medicine 4, Faculty of Medicine, L. Pasteur University Hospital, P. J. Šafárik University in Košice, 041 90 Košice, SlovakiaDepartment of Internal Medicine 4, Faculty of Medicine, L. Pasteur University Hospital, P. J. Šafárik University in Košice, 041 90 Košice, SlovakiaDepartment of Medical Biology, Faculty of Medicine, P. J. Šafárik University in Košice, 040 66 Košice, SlovakiaDepartment of Internal Medicine 4, Faculty of Medicine, L. Pasteur University Hospital, P. J. Šafárik University in Košice, 041 90 Košice, SlovakiaDepartment of Medical Biology, Faculty of Medicine, P. J. Šafárik University in Košice, 040 66 Košice, SlovakiaDepartment of Internal Medicine 4, Faculty of Medicine, L. Pasteur University Hospital, P. J. Šafárik University in Košice, 041 90 Košice, SlovakiaDepartment of Medical Biology, Faculty of Medicine, P. J. Šafárik University in Košice, 040 66 Košice, SlovakiaDepartment of Internal Medicine 4, Faculty of Medicine, L. Pasteur University Hospital, P. J. Šafárik University in Košice, 041 90 Košice, SlovakiaPrevious studies showed associations between variants in TCF7L2 gene and the therapeutic response to sulfonylureas. All sulfonylureas stimulate insulin secretion by the closure of ATP-sensitive potassium (KATP) channel. The aim of the present study was to compare TCF7L2 genotype specific effect of gliclazide binding to KATP channel A-site (Group 1) with sulfonylureas binding to AB-site (Group 2). A total of 101 patients were treated with sulfonylureas for 6 months as an add-on therapy to the previous metformin treatment. TCF7L2 rs7903146 C/T genotype was identified by real-time PCR with subsequent melting curve analysis. Analyses using the dominant genetic model showed significantly higher effect of gliclazide in the CC genotype group in comparison with combined CT + TT genotype group (1.32±0.15% versus 0.73±0.11%, Padj=0.005). No significant difference in ΔHbA1c between the patients with CC genotype and the T-allele carriers was observed in Group 2. In the multivariate analysis, only the TCF7L2 genotype (P=0.006) and the baseline HbA1c (P<0.001) were significant predictors of ΔHbA1c. After introducing an interaction term between the TCF7L2 genotype and the sulfonylurea type into multivariate model, the interaction became a significant predictor (P=0.023) of ΔHbA1c. The results indicate significantly higher difference in ΔHbA1c among the TCF7L2 genotypes in patients treated with gliclazide than in patients treated with glimepiride, glibenclamide, or glipizide.http://dx.doi.org/10.1155/2013/374858 |
| spellingShingle | Martin Javorský Eva Babjaková Lucia Klimčáková Zbynek Schroner Jozef Židzik Mária Štolfová Ján Šalagovič Ivan Tkáč Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide International Journal of Endocrinology |
| title | Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide |
| title_full | Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide |
| title_fullStr | Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide |
| title_full_unstemmed | Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide |
| title_short | Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide |
| title_sort | association between tcf7l2 genotype and glycemic control in diabetic patients treated with gliclazide |
| url | http://dx.doi.org/10.1155/2013/374858 |
| work_keys_str_mv | AT martinjavorsky associationbetweentcf7l2genotypeandglycemiccontrolindiabeticpatientstreatedwithgliclazide AT evababjakova associationbetweentcf7l2genotypeandglycemiccontrolindiabeticpatientstreatedwithgliclazide AT luciaklimcakova associationbetweentcf7l2genotypeandglycemiccontrolindiabeticpatientstreatedwithgliclazide AT zbynekschroner associationbetweentcf7l2genotypeandglycemiccontrolindiabeticpatientstreatedwithgliclazide AT jozefzidzik associationbetweentcf7l2genotypeandglycemiccontrolindiabeticpatientstreatedwithgliclazide AT mariastolfova associationbetweentcf7l2genotypeandglycemiccontrolindiabeticpatientstreatedwithgliclazide AT jansalagovic associationbetweentcf7l2genotypeandglycemiccontrolindiabeticpatientstreatedwithgliclazide AT ivantkac associationbetweentcf7l2genotypeandglycemiccontrolindiabeticpatientstreatedwithgliclazide |