Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes
The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7 like 2 gene (TCF7L2) is the strongest genetic risk factor associated with T2D to date. In this study we explor...
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doaj-f4eeead7bc3e4f349eb99895e8c00ad52020-11-25T00:52:24ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBosnian Journal of Basic Medical Sciences1512-86011840-48122019-05-0110.17305/bjbms.2019.4181Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetesTanja Dujic0Tamer Bego1Maja Malenica2Zelija Velija-Asimi3Emma Ahlqvist4Leif Groop5Ewan R. Pearson6Adlija Causevic7Sabina Semiz8Department of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and HerzegovinaDepartment of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and HerzegovinaDepartment of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and HerzegovinaFaculty of Medicine, University of Sarajevo, Sarajevo, Bosnia and HerzegovinaLund University Diabetes Centre, Lund University, Malmö, SwedenLund University Diabetes Centre, Lund University, Malmö, SwedenDivision of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, Scotland, UKDepartment of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and HerzegovinaDepartment of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina; Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7 like 2 gene (TCF7L2) is the strongest genetic risk factor associated with T2D to date. In this study we explored the effects of TCF7L2 rs7903146 genotype on metformin response in T2D. The study included 86 newly diagnosed patients with T2D, incident users of metformin. Levels of fasting glucose, insulin, HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and anthropometric parameters were measured prior to metformin therapy, and 6 and 12 months after the treatment. Genotyping of TCF7L2 rs7903146 was performed by the Sequenom MassARRAY® iPLEX® platform. At baseline, the diabetes risk allele (T) showed an association with lower triglyceride levels (p = 0.037). After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9-38.3%, p = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1-44.1%, p = 0.005), after adjustment for baseline values. Moreover, the T allele was associated with 6.7% lower fasting glucose levels (95% CI 1.1-12.0%, p = 0.021), adjusted for baseline glucose and baseline HOMA-%B levels, after 6 months of metformin treatment. This effect was more pronounced in TT carriers who had 16.8% lower fasting glucose levels (95% CI 7.0-25.6%, p = 0.002) compared to the patients with CC genotype. Our results suggest that TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment. http://www.bjbms.org/ojs/index.php/bjbms/article/view/4181Metformintype 2 diabetespharmacogeneticstranscription factor 7 like 2 geneTCF7L2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tanja Dujic Tamer Bego Maja Malenica Zelija Velija-Asimi Emma Ahlqvist Leif Groop Ewan R. Pearson Adlija Causevic Sabina Semiz |
spellingShingle |
Tanja Dujic Tamer Bego Maja Malenica Zelija Velija-Asimi Emma Ahlqvist Leif Groop Ewan R. Pearson Adlija Causevic Sabina Semiz Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes Bosnian Journal of Basic Medical Sciences Metformin type 2 diabetes pharmacogenetics transcription factor 7 like 2 gene TCF7L2 |
author_facet |
Tanja Dujic Tamer Bego Maja Malenica Zelija Velija-Asimi Emma Ahlqvist Leif Groop Ewan R. Pearson Adlija Causevic Sabina Semiz |
author_sort |
Tanja Dujic |
title |
Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes |
title_short |
Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes |
title_full |
Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes |
title_fullStr |
Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes |
title_full_unstemmed |
Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes |
title_sort |
effects of tcf7l2 rs7903146 variant on metformin response in patients with type 2 diabetes |
publisher |
Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
series |
Bosnian Journal of Basic Medical Sciences |
issn |
1512-8601 1840-4812 |
publishDate |
2019-05-01 |
description |
The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7 like 2 gene (TCF7L2) is the strongest genetic risk factor associated with T2D to date. In this study we explored the effects of TCF7L2 rs7903146 genotype on metformin response in T2D. The study included 86 newly diagnosed patients with T2D, incident users of metformin. Levels of fasting glucose, insulin, HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and anthropometric parameters were measured prior to metformin therapy, and 6 and 12 months after the treatment. Genotyping of TCF7L2 rs7903146 was performed by the Sequenom MassARRAY® iPLEX® platform. At baseline, the diabetes risk allele (T) showed an association with lower triglyceride levels (p = 0.037). After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9-38.3%, p = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1-44.1%, p = 0.005), after adjustment for baseline values. Moreover, the T allele was associated with 6.7% lower fasting glucose levels (95% CI 1.1-12.0%, p = 0.021), adjusted for baseline glucose and baseline HOMA-%B levels, after 6 months of metformin treatment. This effect was more pronounced in TT carriers who had 16.8% lower fasting glucose levels (95% CI 7.0-25.6%, p = 0.002) compared to the patients with CC genotype. Our results suggest that TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.
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topic |
Metformin type 2 diabetes pharmacogenetics transcription factor 7 like 2 gene TCF7L2 |
url |
http://www.bjbms.org/ojs/index.php/bjbms/article/view/4181 |
work_keys_str_mv |
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