Genetic Architecture of Type 2 Diabetes: Recent Progress and Clinical Implications

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Genetic Architecture of Type 2 Diabetes: Recent Progress and Clinical Implications

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Title: Genetic Architecture of Type 2 Diabetes: Recent Progress and Clinical Implications
Author: Moore, Allan F.; Grant, Richard William; Florez, Jose Carlos

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Citation: Grant, Richard W., Allan F. Moore, and Jose C. Florez. 2009. Genetic architecture of type 2 diabetes: Recent progress and clinical implications. Diabetes Care 32(6): 1107-1114.
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Abstract: Review. Introductory paragraph: With the exception of rare monogenic disorders, most type 2 diabetes results from the interaction of genetic variation at multiple different chromosomal sites with environmental exposures experienced throughout the lifespan (1). This complex genetic architecture has important consequences for understanding the pathophysiology of type 2 diabetes, both for researchers seeking mechanistic insight into disease progression and for clinicians hoping to translate this new genetic information into more effective patient management. With nearly two dozen genes associated with type 2 diabetes, including some genetic variants that appear to modify responses to commonly prescribed diabetes medications and lifestyle interventions, we may be on the verge of a new era in which a patient’s individual genetic profile can add useful information to clinical care. Indeed, commercial companies are already offering genome-wide genetic profiling that includes information related to diabetes risk (2). Further advances in type 2 diabetes genetic discovery hold the promise, as yet unrealized, of enabling clinicians to individualize care for their patients by basing their clinical decisions on patient risk for disease progression, propensity to develop specific complications, and likely response to different medication classes. At present it is unknown whether individual genetic information may also serve to effectively motivate patient behavior change, a cornerstone of diabetes and pre-diabetes management. In this review of polygenic type 2 diabetes, we focus on recent discoveries made via linkage analyses, candidate gene association studies and genome-wide association (GWA) scans and highlight potential clinical applications of new genetic knowledge to risk prediction, pharmacologic management, and patient behavior. Monogenic diabetes has recently been reviewed elsewhere (3).
Published Version: doi:10.2337/dc08-2171
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