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Recent research reveals that a rogue's gallery of genes may be involved in the development of type 2 diabetes. The findings lend insight into how those genes may interact in the chronic multifactor illness.
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"You have a mix of genetics and environment, and the genetics are really messy" in type 2 diabetes, explained Francis Collins, MD, director of the National Human Genome Research Institute, at the American Diabetes Association's 67th Scientific Sessions, held June 22–26 in Chicago.
The new tools of molecular biology first identified single defective genes responsible for diseases such as cystic fibrosis, says Collins. Now multiple genes are being tagged for involvement in type 2 diabetes: An international research consortium has linked seven genes to the disease. Three others—PPAR(G), KCNJ11, and TCF7L2—had been previously found.1–3
The research consortium identified the seven new genes in a study of genetic variability among >32,000 people in four population groups:
Gene Breakthroughs
Asian, African, American, and European. Collectively, the 10 genes account for about 80% of the risk of type 2 diabetes, though they have modest individual effects, researchers say. Most likely, more genes related to diabetes remain to be found, says Collins.
GENETIC INSIGHTS
Discovery of the genes will shed light on how diabetes arises and is
related to other metabolic risks, Collins says. One of the genes, GCKR, is
also linked to the regulation of triglycerides. Another, SLC30A8, produces a
protein involved in transporting zinc into pancreatic beta-cells.
Although treating type 2 diabetes by correcting genetic defects is on the distant horizon, knowledge of the genes may still benefit patients in the near term. Specifically, the knowledge is spurring the development of new genotyping tests to better assess individual risk. One such test was recently introduced to the market by deCODE Genetics.
Genotyping tests are useful for differentiating diseases that appear superficially similar; they have identified subtypes of breast, prostate, and colon cancer. Similarly, genotyping may well break type 2 diabetes into subtypes that are amenable to different therapies.
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In addition, the discovery of diabetes-related genes and their protein products may lead to better-targeted drug treatments, Collins says. Future generations of drugs will likely be able to more closely mirror naturally occurring molecules and processes, presumably with greater efficacy and fewer side effects, experts suggest.
THE VALUE OF `JUNK DNA'
Another important study indicates that disease may depend on more than the
presence or absence of a particular gene, notes Collins.
For years, scientists have been puzzled by how little of the human genome actually codes for genes. Less than 2% of the human genome contains genes, with vast segments composed of repeated sequences considered "junk DNA," according to researchers.
An international group called the Encyclopedia of DNA Elements (ENCODE) performed an exhaustive, in-depth 4-year analysis of 1% of the human genome to list all of its biologically functional elements.4
The group discovered that the so-called junk DNA actually has a profound role in regulating and amplifying nearby genes. This finding may explain how genes with weak effects can lead to a disease such as diabetes, says Collins.
"We shouldn't be calling the noncoding portion of the genome
`junk,'" adds Collins. "It seems to carry within it variations
that confer a risk of disease." 
Footnotes
Further description of the latest research findings on type 2 diabetes and genetic risk is available from the National Institutes of Health (NIH) at www.genome.gov/25521010.
For patients with questions about genes and genetic testing, information is available from NIH at www.genome.gov/19016903.
NIH offers an online education kit, "Understanding the Human Genome Project," at www.genome.gov/25019879.
References
2. Zeggini E, Weedon MN, Lindgren CM, et al.: Replication of
genome-wide association signals in U.K. samples reveals risk loci for type 2
diabetes. Science 316:1336–1341, 2007.
3. Scott LJ, Mohlke KL, Bonnycastle LL, et al.: A genome-wide
association study of type 2 diabetes in Finns detects multiple susceptibility
variants. Science 316:1341–1345, 2007.
4. The ENCODE Project Consortium: Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816, 2007.[Medline]
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