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 explo...
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| Format: | Article |
| Language: | English |
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Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
2019-11-01
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| Series: | Biomolecules & Biomedicine |
| Subjects: | |
| Online Access: | https://www.bjbms.org/ojs/index.php/bjbms/article/view/4181 |
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| author | Tanja Dujic Tamer Bego Maja Malenica Zelija Velija-Asimi Emma Ahlqvist Leif Groop Ewan R. Pearson Adlija Causevic Sabina Semiz |
| 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 |
| collection | DOAJ |
| 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 the 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 the 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 the 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 the 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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| first_indexed | 2024-04-24T23:33:02Z |
| format | Article |
| id | doaj.art-f4eeead7bc3e4f349eb99895e8c00ad5 |
| institution | Directory Open Access Journal |
| issn | 2831-0896 2831-090X |
| language | English |
| last_indexed | 2024-04-24T23:33:02Z |
| publishDate | 2019-11-01 |
| publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
| record_format | Article |
| series | Biomolecules & Biomedicine |
| spelling | doaj.art-f4eeead7bc3e4f349eb99895e8c00ad52024-03-15T14:30:12ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBiomolecules & Biomedicine2831-08962831-090X2019-11-0119410.17305/bjbms.2019.4181Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetesTanja Dujic0https://orcid.org/0000-0001-9221-1208Tamer Bego1https://orcid.org/0000-0002-6424-6945Maja Malenica2Zelija Velija-Asimi3https://orcid.org/0000-0003-2014-248XEmma Ahlqvist4https://orcid.org/0000-0002-6513-2384Leif Groop5Ewan R. Pearson6Adlija Causevic7https://orcid.org/0000-0002-2203-0871Sabina Semiz8https://orcid.org/0000-0003-2629-4660Department 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 HerzegovinaDepartment of Internal Medicine, Faculty 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 the 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 the 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 the 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 the 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. https://www.bjbms.org/ojs/index.php/bjbms/article/view/4181Metformintype 2 diabetespharmacogeneticstranscription factor 7-like 2 geneTCF7L2 |
| 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 Biomolecules & Biomedicine Metformin type 2 diabetes pharmacogenetics transcription factor 7-like 2 gene TCF7L2 |
| title | 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_short | 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 |
| topic | Metformin type 2 diabetes pharmacogenetics transcription factor 7-like 2 gene TCF7L2 |
| url | https://www.bjbms.org/ojs/index.php/bjbms/article/view/4181 |
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