The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Variation in TCF7L2 Influences Therapeutic Response to Sulfonylureas
Open accessAbstract
OBJECTIVE— There is considerable interindividual variation in sulfonylurea response in type 2 diabetes. Transcription factor 7-like 2 (TCF7L2) variants have been identified to be strongly associated with type 2 diabetes risk, probably due to decreased β-cell function. We hypothesized that variation in TCF7L2 would influence response to sulfonylureas but not metformin. We studied the effect of TCF7L2 rs12255372 and rs7903146 genotypes on glycemic response. RESEARCH DESIGN AND METHODS— The DARTS/MEMO (Diabetes Audit and Research Tayside/Medicines Monitoring Unit) collaboration database includes prescribing, biochemistry, and clinical phenotype of all patients with diabetes within Tayside, Scotland, from 1992. Of these, the TCF7L2 genotype was determined in 4,469 patients with type 2 diabetes recruited to GoDARTS (Genetics of Diabetes Audit and Research Tayside) between 1997 and July 2006. A total of 901 incident sulfonylurea users and 945 metformin users were identified. A logistic regression was used with treatment failure defined as an A1C >7% within 3–12 months after treatment initiation. Covariates included the TCF7L2 genotype, BMI, sex, age diagnosed, drug adherence, and drug dose. A1C pretreatment was available in a subset of patients (sulfonylurea n = 579; metformin n = 755). RESULTS— Carriers of the risk allele were less likely to respond to sulfonylureas with an odds ratio (OR) for failure of 1.95 (95% CI 1.23–3.06; P = 0.005), comparing rs12255372 T/T vs. G/G. Including the baseline A1C strengthened this association (OR 2.16 [95% CI 1.21–3.86], P = 0.009). A similar, although slightly weaker, association was seen with rs7903146. No association was seen between metformin response and either single nucleotide polymorphism, after adjustment for baseline A1C. CONCLUSIONS— TCF7L2 variants influence therapeutic response to sulfonylureas but not metformin. This study establishes that genetic variation can alter response to therapy in type 2 diabetes.
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Cites
A genome-wide association study identifies novel risk loci for type 2 diabetes
Sladek, R., Rocheleau, G., Rung, J., Dina, C., Shen, L., Serre, D., Boutin, P., Vincent, D., Belisle, A., Hadjadj, S., et al. (2007) · Nature · doi:10.1038/nature05616 · Cited by 2,993
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes
Grant, S. F. A., Thorleifsson, G., Reynisdottir, I., Benediktsson, R., Manolescu, A., Sainz, J., Helgason, A., Stefansson, H., Emilsson, V., Helgadottir, A., et al. (2006) · Nature Genetics · doi:10.1038/ng1732 · Cited by 2,287
Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations
Pearson, E. R., Flechtner, I., Njølstad, P. R., Malecki, M. T., Flanagan, S. E., Larkin, B., Ashcroft, F. M., Klimes, I., Codner, E., Iotova, V., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061759 · Cited by 988
Self-citationTCF7L2 Polymorphisms and Progression to Diabetes in the Diabetes Prevention Program
Florez, J. C., Jablonski, K. A., Bayley, N., Pollin, T. I., de Bakker, P. I. W., Shuldiner, A. R., Knowler, W. C., Nathan, D. M., & Altshuler, D. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa062418 · Cited by 839
Genetic cause of hyperglycaemia and response to treatment in diabetes
Pearson, E. R., Starkey, B. J., Powell, R. J., Gribble, F. M., Clark, P. M., & Hattersley, A. T. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14571-0 · Cited by 607
Self-citationRefining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution
Helgason, A., Pálsson, S., Thorleifsson, G., Grant, S. F. A., Emilsson, V., Gunnarsdottir, S., Adeyemo, A., Chen, Y., Chen, G., Reynisdottir, I., et al. (2007) · Nature Genetics · doi:10.1038/ng1960 · Cited by 525
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Self-citationDonnan, P. T., MacDonald, T. M., & Morris, A. D. (2002) · Diabetic Medicine · doi:10.1046/j.1464-5491.2002.00689.x · Cited by 437
Self-citationSCHEINFELD, A. (1945) · The American Journal of the Medical Sciences · doi:10.1097/00000441-194507000-00025 · Cited by 380
Saxena, R., Gianniny, L., Burtt, N. P., Lyssenko, V., Giuducci, C., Sjögren, M., Florez, J. C., Almgren, P., Isomaa, B., Orho-Melander, M., et al. (2006) · Diabetes · doi:10.2337/db06-0381 · Cited by 374
Cited by
Genomics, type 2 diabetes, and obesity
McCarthy, M. I. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0906948 · Cited by 938
Self-citationInsulin gene mutations as a cause of permanent neonatal diabetes
Støy, J., Edghill, E. L., Flanagan, S. E., Ye, H., Paz, V. P., Pluzhnikov, A., Below, J. E., Hayes, M. G., Cox, N. J., Lipkind, G. M., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707291104 · Cited by 564
Self-citationChung, W. K., Erion, K., Florez, J. C., Hattersley, A. T., Hivert, M.-F., Lee, C. G., McCarthy, M. I., Nolan, J. J., Norris, J. M., Pearson, E. R., et al. (2020) · Diabetes Care · doi:10.2337/dci20-0022 · Cited by 400
The genetic and epigenetic basis of type 2 diabetes and obesity
Drong, A. W., Lindgren, C. M., & McCarthy, M. I. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.149 · Cited by 212
Self-citationChung, W. K., Erion, K., Florez, J. C., Hattersley, A. T., Hivert, M.-F., Lee, C. G., McCarthy, M. I., Nolan, J. J., Norris, J. M., Pearson, E. R., et al. (2020) · Diabetologia · doi:10.1007/s00125-020-05181-w · Cited by 203
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Metadata
- Authors
- Pearson, E. R., Donnelly, L. A., Kimber, C., Whitley, A., Doney, A. S. F., McCarthy, M. I., Hattersley, A. T., Morris, A. D., & Palmer, C. N. A.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2007-08-01
- Volume
- 56
- Issue
- 8
- Pages
- 2178-2182
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2124088457
- Cited by
- 286
- References
- 29
- FWCI
- 13.90
- Type
- journal article
- Language
- en
- Open access
- bronze
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