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HuGENet™ Case Study

Evaluation of the TCF7L2 gene as a predictor of type 2 diabetes

A. Cecile J.W. Janssens, PhD
Center for Medical Decision Making
Department of Public Health
Erasmus University Medical Center Rotterdam, the Netherlands

Educational objectives

After reading this case study, you should be able to:

  • interpret gene-disease associations in terms of clinical validity of a genetic test
  • calculate basic indicators of clinical validity and utility
  • discuss the potential clinical or public health implications of predictive testing based on a single disease susceptibility gene.

    Introduction

    Type 2 diabetes mellitus represents a significant health problem in the United States. According to the most recent assessment by the Centers for Disease Control and Prevention (CDC), the prevalence of type 2 diabetes is nearly 6% nationwide; prevalence exceeds 10% in some ethnic subgroups, including African-Americans, Hispanics and Native Americans. Although the risk of type 2 diabetes increases with age, incidence has been rising in all age groups and the increase in children is of particular concern. In 2000, diabetes was the sixth leading cause of death.

    In type 2 diabetes, the body’s impaired production and use of insulin results in chronically elevated blood glucose levels and long-term tissue damage. Evidence for genetic susceptibility to type 2 diabetes comes from studies of population admixture, familial aggregation, mono- and dizygotic twins, and genetic association and linkage. Diabetes is also a major feature of certain monogenic disorders including maturity-onset diabetes of the young (MODY). Genome-wide linkage studies have identified susceptibility loci for type 2 diabetes on many chromosomes and associations with numerous candidate genes (including mitochondrial genes) have been reported. Most of these associations are small (OR 1-2) and inconsistent among studies.

    Case Study

    In February 2006, Grant et al. reported that a variant of the TCF7L2 gene is associated with type 2 diabetes (T2D).

    Grant SF, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 2006;38:320-323.

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