*This test is not yet approved for patients in New York, California, Pennsylvania, or Maryland.
deCODE T2™ is the first test available to predict the risk for type 2 diabetes based on common genetic variants.
This test determines the alleles present for four different SNPs (single nucleotide polymorphisms) in or near the TCF7L2, CDKAL1, PPARG, and CDKN2A genes. SNPs are common variations in the genome – each occurring in at least 1% of the population. These common variations are becoming increasingly useful for predicting the risk for common diseases. Research has been complicated by the fact that most variants exert a relatively small effect, so that very large populations must be studied in order to detect and replicate associations.
The deCODE T2™ variants have now been confirmed by independent research groups involving tens of thousands of patients from diverse populations.
TCF7L2
In 2006, scientists at deCODE Genetics discovered that individuals with two copies of the”T” allele (one on each chromosome) in the transcription factor 7-like 2 (TCF7L2) gene have a two-fold increased risk for developing type 2 diabetes compared to individuals with no T allele.1 Approximately 10% of European Caucasians have two copies of this variant.2 At least 40 different studies representing diverse populations have now confirmed the association. While the allele frequencies vary considerably between populations, the impact on diabetes risk is remarkably consistent. This association appears to be the result of decreased beta-cell function. The TCF7L2 variant remains the single strongest and most researched type 2 diabetes risk marker.
CDKAL1
In 2007, deCODE Genetics reported that the “C” allele of a SNP in the CDKAL1 gene was associated with an increased type 2 diabetes risk. The odds ratio in European and Chinese ancestry populations was about 1.2 for individuals with one C allele and about 1.5 for those with two.3
PPARG
The “C” allele of the PPARG gene has been shown to increase the risk for type 2 diabetes in multiple different studies. Interestingly, the C allele is the most common form of the gene with an allele frequency of about 85%. Each C allele present increases the risk of type 2 diabetes about 1.14 fold4,5,6,7.
CDKN2A
The “T” allele of a SNP near the CDKN2A gene was found to be associated with an increased risk for type 2 diabetes by three different genome-wide association studied published in 2007 (odds ratios about 1.20)5,6,7. The SNP is not within a currently recognized gene and the mechanism of action is not currently understood.
Laboratory: Testing is performed by deCODE Genetics, a CLIA-certified reference laboratory.
Methodology: Genotyping by Centaurus™ SNP Assay
This test was developed and its performance characteristics determined by the deCODE Genetics Reference Laboratory. It is not required to go through pre-market FDA review and, like most genetic tests, has not been cleared or approved by the FDA.
1. Grant SF, Thorleifsson G, Reynisdottir I, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006;38(3):320-3.
2. Weedon MN. The importance of TCF7L2. Diabet Med. 2007;24(10):1062-6.
3. Steinthorsdottir V, Thorleifsson G, Reynisdottir I, et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet. 2007 Jun;39(6):770-5.
4. Altshuler D, Hirschhorn JN, Klannemark M, et al. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet. 2000;26(1):76-80.
5. Zeggini E, Weedon MN, Lindgren CM, et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007;316(5829):1336-41.
6. Scott LJ, Mohlke KL, Bonnycastle LL, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007;316(5829):1341-5.
7. Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research, et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science. 2007;316(5829):1331-6.