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Diabetologia
Published in: Diabetologia 1/2007

Open Access 01-01-2007 | Commentary

TCF7L2: the biggest story in diabetes genetics since HLA?

Authors: E. Zeggini, M. I. McCarthy

Published in: Diabetologia | Issue 1/2007

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Excerpt

Much has been made over the past decade of the potential for genetics to advance our understanding of the pathogenesis of type 2 diabetes and to ‘revolutionise’ management of this condition [1]. Others have argued that these claims are premature [2]; indeed, some have questioned the contribution of genetic predisposition to the pathogenesis of common forms of type 2 diabetes [3]. …
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Pearson ER, Flechtner I, Njolstad PR et al (2006) Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med 355:467–477PubMedCrossRef
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McCarthy MI (2004) Progress in defining the molecular basis of type 2 diabetes mellitus through susceptibility-gene identification. Hum Mol Genet 13:R33–R41PubMedCrossRef
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Hattersley AT, McCarthy MI (2005) A question of standards: what makes a good genetic association study? Lancet 366:1315–1323PubMedCrossRef
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Gloyn AL, Weedon MN, Owen KR et al (2003) Large scale association studies of variants in genes encoding the pancreatic beta-cell K-ATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with increased risk of Type 2 Diabetes. Diabetes 52:568–572PubMed
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van Vliet-Ostaptchouk JV, Shiri-Sverdlov R, Zhernakova A et al (2007) Association of variants of transcription factor 7-like 2 (TCF7L2) with susceptibility to type 2 diabetes in the Dutch Breda cohort. Diabetologia. DOI 10.​1007/​s00125-006-0477-z
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Chandak GR, Janipalli CS, Bhaskar S et al (2007) Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population, Diabetologia. DOI 10.​1007/​s00125-006-0502-2
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Groves CJ, Zeggini E, Minton J et al (2006) Association analysis of 6736 UK subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk. Diabetes 55:2640–2644PubMedCrossRef
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Florez JC, Jablonski KA, Bayley N et al (2006)TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med 355:241–250PubMedCrossRef
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Damcott CM, Pollin TI, Reinhard LJ et al (2006) Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish: replication and evidence for a role in both insulin secretion and insulin resistance. Diabetes 55:2654–2659PubMedCrossRef
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Scott LJ, Bonnycastle C, Willer CJ et al (2006) Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample. Diabetes 55:2649–2653PubMedCrossRef
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Cauchi S, Meyre D, Dina C et al (2006) Transcription factor TCF7L2 genetic study in the French population: expression in human β-cells and adipose tissue and strong association with type 2 diabetes. Diabetes 55:2903–2908PubMedCrossRef
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Wiltshire S, Hattersley AT, Hitman GA et al (2001) A genomewide scan for loci predisposing to type 2 diabetes in a U.K. population (the Diabetes UK Warren 2 Repository): analysis of 573 pedigrees provides independent replication of a susceptibility locus on chromosome 1q. Am J Hum Genet 69:553–569PubMedCrossRef
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Cauchi S, Vaxillaire M, Choquet H et al (2007) No major contribution of TCFL2 sequence variants to maturity onset of diabetes of the young (MODY) or neonatal diabetes mellitus in French white subjects. Diabetologia. DOI 10.​1007/​s00125-006-0505-z
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Field SF, Howson JMM, Smyth DJ, Walker NM, Dunger DB, Todd JA (2007) Analysis of the type 2 diabetes gene, TCF7L2, in 13,795 type 1 diabetes cases and control subjects. Diabetologia. DOI 10.​1007/​s00125-006-0506-y
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Weedon MN, McCarthy MI, Hitman G et al (2006) Combining information from multiple common susceptibility polymorphisms increases the predictive power of genetic information: a study of replicated type 2 diabetes variants. PLoS Med 3:e374PubMedCrossRef
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Metadata
Title
TCF7L2: the biggest story in diabetes genetics since HLA?
Authors
E. Zeggini
M. I. McCarthy
Publication date
01-01-2007
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 1/2007
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0507-x

Other articles of this Issue 1/2007

Diabetologia 1/2007 Go to the issue

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No major contribution of TCF7L2 sequence variants to maturity onset of diabetes of the young (MODY) or neonatal diabetes mellitus in French white subjects

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Human evidence for the involvement of insulin-induced gene 1 in the regulation of plasma glucose concentration

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Association of variants of transcription factor 7-like 2 (TCF7L2) with susceptibility to type 2 diabetes in the Dutch Breda cohort

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Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects

Letter

Comment on: Nathan DM, Buse JB, Davidson MB et al (2006) Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 49: 1711–1721
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