Multiple genetic testing for susceptibility to common disease: PPARG and CAPN10 SNP’s and 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, such as sensitivity, specificity and area under the receiver operating characteristic curve (AUC)
  • discuss the potential clinical or public health impact of genetic testing multiple disease susceptibility genes.


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 December 2005, Lyssenko et al. reported significant associations of the PPARG PP and CAPN10 SNP43/44 GG/TT genotypes with type 2 diabetes (T2D). They suggested that genetic testing for these variants might offer a future approach to identifying individuals at risk of T2D.

Lyssenko V, Almgren P, Anevski D, Orho-Melander M, Sjogren M et al. (2005) Genetic prediction of future type 2 diabetesExternal. PLoS Medicine 2: e345
You can view this quiz in html format.

The results of this exercise have been published as a letter to the editor in PLoS Medicine, including a response of the authors.

Janssens ACJW, Gwinn M, Subramonia-Iyer S, Khoury MJ. Does genetic testing really improve the prediction of future type 2 diabetes? PLOS Medicine 2006; 2:E114.


Author’s reply:

Page last reviewed: June 15, 2009 (archived document)