The importance of TCF7L2

After many years of frustratingly limited success, the genetic architecture of Type 2 diabetes is finally being uncovered. Recent genome‐wide association studies have identified novel genes predisposing to Type 2 diabetes, which are giving fascinating new insights into the pathophysiology of this complex disease. Of the genes so far identified by this approach, one stands out as having by far the biggest effect on disease risk. A common variant of TCF7L2, when present in two copies, is associated with an approximate 2‐fold higher risk of Type 2 diabetes. This short review focuses on the TCF7L2 finding and discusses its significance for Type 2 diabetes genetic studies and for clinical practice.

[1]  Mark Walker,et al.  Combining Information from Common Type 2 Diabetes Risk Polymorphisms Improves Disease Prediction , 2006, PLoS medicine.

[2]  Philippe Froguel,et al.  TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis , 2007, Journal of Molecular Medicine.

[3]  Muin J Khoury,et al.  Predictive genetic testing for type 2 diabetes , 2006, BMJ : British Medical Journal.

[4]  Laura J. Scott,et al.  Association of Transcription Factor 7-Like 2 (TCF7L2) Variants With Type 2 Diabetes in a Finnish Sample , 2006, Diabetes.

[5]  Inês Barroso,et al.  TCF7L2 Polymorphisms Modulate Proinsulin Levels and β-Cell Function in a British Europid Population , 2007, Diabetes.

[6]  J. Gulcher,et al.  A variant in CDKAL1 influences insulin response and risk of type 2 diabetes , 2007, Nature Genetics.

[7]  H. Stefánsson,et al.  Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes , 2006, Nature Genetics.

[8]  G. Hunter,et al.  Polymorphism in the Transcription Factor 7-Like 2 (TCF7L2) Gene Is Associated With Reduced Insulin Secretion in Nondiabetic Women , 2006, Diabetes.

[9]  Steven Wiltshire,et al.  Association Analysis of 6,736 U.K. Subjects Provides Replication and Confirms TCF7L2 as a Type 2 Diabetes Susceptibility Gene With a Substantial Effect on Individual Risk , 2006, Diabetes.

[10]  J. Gulcher,et al.  Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution , 2007, Nature Genetics.

[11]  U. Smith TCF7L2 and type 2 diabetes—we WNT to know , 2006, Diabetologia.

[12]  G. Abecasis,et al.  A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants , 2007, Science.

[13]  M. McCarthy,et al.  Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes , 2007, Science.

[14]  Muin J Khoury,et al.  Improving the prediction of complex diseases by testing for multiple disease-susceptibility genes. , 2003, American journal of human genetics.

[15]  H. Edlund,et al.  Attenuated Wnt signaling perturbs pancreatic growth but not pancreatic function. , 2005, Diabetes.

[16]  David M Nathan,et al.  TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. , 2006, The New England journal of medicine.

[17]  M. Jarvelin,et al.  Type 2 diabetes TCF7L2 risk genotypes alter birth weight: a study of 24,053 individuals. , 2007, American journal of human genetics.

[18]  S. Fowler,et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. , 2002 .

[19]  K. Silver,et al.  Polymorphisms in the Transcription Factor 7-Like 2 (TCF7L2) Gene Are Associated With Type 2 Diabetes in the Amish , 2006, Diabetes.

[20]  A. Hattersley,et al.  Genetic cause of hyperglycaemia and response to treatment in diabetes , 2003, The Lancet.

[21]  C. Dina,et al.  TCF7L2 Variation Predicts Hyperglycemia Incidence in a French General Population , 2006, Diabetes.

[22]  R. Duggirala,et al.  Haplotypes of Transcription Factor 7–Like 2 (TCF7L2) Gene and Its Upstream Region Are Associated With Type 2 Diabetes and Age of Onset in Mexican Americans , 2007, Diabetes.

[23]  M. Khoury,et al.  How many genes underlie the occurrence of common complex diseases in the population? , 2005, International journal of epidemiology.

[24]  D. Heath,et al.  Expression Profiling and Functional Analysis of Wnt Signaling Mechanisms in Mesenchymal Stem Cells , 2004, Stem cells.

[25]  F. Ashcroft,et al.  Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. , 2006, The New England journal of medicine.

[26]  Kristin G Ardlie,et al.  Common Single Nucleotide Polymorphisms in TCF7L2 Are Reproducibly Associated With Type 2 Diabetes and Reduce the Insulin Response to Glucose in Nondiabetic Individuals , 2006, Diabetes.

[27]  W. Rathmann,et al.  Variants of the Transcription Factor 7-Like 2 Gene (TCF7L2) are Strongly Associated with Type 2 Diabetes but not with the Metabolic Syndrome in the MONICA/KORA Surveys , 2007, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[28]  M. McCarthy,et al.  Common variants in WFS1 confer risk of type 2 diabetes , 2007, Nature Genetics.

[29]  P. Froguel,et al.  A genetic variation of the transcription factor 7-like 2 gene is associated with risk of type 2 diabetes in the Japanese population , 2007, Diabetologia.

[30]  Y. Iwamoto,et al.  Replication study for the association of TCF7L2 with susceptibility to type 2 diabetes in a Japanese population , 2007, Diabetologia.

[31]  S. R. Kulkarni,et al.  Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population , 2006, Diabetologia.

[32]  E. Steyerberg,et al.  Revisiting the clinical validity of multiplex genetic testing in complex diseases. , 2004, American journal of human genetics.

[33]  T. Hudson,et al.  A genome-wide association study identifies novel risk loci for type 2 diabetes , 2007, Nature.

[34]  Marcia M. Nizzari,et al.  Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels , 2007, Science.