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J Clin Endocrinol Metab. 2008 Dec;93(12):4633-42. doi: 10.1210/jc.2008-1345. Epub 2008 Sep 9.

Clinical review: the genetics of type 2 diabetes: a realistic appraisal in 2008.

Author information

1
Simches Research Building-CPZN 5.250, 185 Cambridge Street, Diabetes Unit/Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. jcflorez@partners.org

Abstract

CONTEXT:

Over the last few months, genome-wide association studies have contributed significantly to our understanding of the genetic architecture of type 2 diabetes. If and how this information will impact clinical practice is not yet clear.

EVIDENCE ACQUISITION:

Primary papers reporting genome-wide association studies in type 2 diabetes or establishing a reproducible association for specific candidate genes were compiled. Further information was obtained from background articles, authoritative reviews, and relevant meeting conferences and abstracts.

EVIDENCE SYNTHESIS:

As many as 17 genetic loci have been convincingly associated with type 2 diabetes; 14 of these were not previously known, and most of them were unsuspected. The associated polymorphisms are common in populations of European descent but have modest effects on risk. These loci highlight new areas for biological exploration and allow the initiation of experiments designed to develop prediction models and test possible pharmacogenetic and other applications.

CONCLUSIONS:

Although substantial progress in our knowledge of the genetic basis of type 2 diabetes is taking place, these new discoveries represent but a small proportion of the genetic variation underlying the susceptibility to this disorder. Major work is still required to identify the causal variants, test their role in disease prediction and ascertain their therapeutic implications.

PMID:
18782870
PMCID:
PMC2626447
DOI:
10.1210/jc.2008-1345
[Indexed for MEDLINE]
Free PMC Article

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