Seven Newly-Identified Diabetes Genes

By : Pat Carpenter
Recent research findings may offer some new hope to 20.8 million individuals in Dallas, Houston, elsewhere in Texas and throughout the rest of the United States who have diabetes. While an estimated 14.6 million have been diagnosed, 6.2 million people (or nearly one-third) are unfortunately unaware that they have the disease.

Researchers recently identified seven new genes connected to the most common form of diabetes. The findings, presented in three reports by university scientists and one by a private company, offer novel insights into the biology of a disease that affects 170 million people worldwide.

The reports bring the number of well-attested genes involved in adult-onset, or Type 2 diabetes up to 10, from the three known previously. The new genes do not immediately suggest any new therapy, but may point to a new biological basis for the disease, from which effective treatments could emerge in time.

DeCode Genetics, an Icelandic company responsible for one of the reports, has dominated the genetic-research field for the past five years. The other papers come from three academic consortia, led by Dr. David Altshuler of the Broad Institute, Michael Boehnke of the University of Michigan and Mark McCarthy of the University of Oxford in England.

Several researchers said that the new diabetes studies, and a soon-to-be-released report on seven major diseases prepared by the Welcome Trust in London, were a turning point in the pursuit of the genes that underlie common diseases like diabetes, cardiovascular disease, cancer and schizophrenia. The variant genes are common, but each makes only a small contribution to disease, rendering them hard to identify.

There is considerable overlap in the diabetes genes identified in the recent four reports, giving the authors confidence that at last their whole genome association method is producing reliable results.

Until recently, "there was no sense of progress" in tracking down the genes of diabetes or other common diseases, Dr. Altshuler said. The logjam started to break a year ago with DeCode's report of its TCF7L2 gene, and the consistent findings reported by the academic centers "has to be acknowledged as substantial progress," Dr. Altshuler said.

Dr. Boehnke agreed, saying, "It's very exciting to have results in which we truly believe." Up until now, he said, diabetes research has been what his professor warned would be "a geneticist's nightmare."

The importance of the new genes is that they point to previously unknown pathways involved in diabetes. Dr. Altshuler agreed with Dr. Stefansson's view that DeCode's TCF7L2 gene has the greatest effect on diabetes, but said the other genes provide new insights regardless of the size of their effects. "The fact that none of the genes found were on anyone's radar screen shows how much there is to learn," Dr. Altshuler said.

"I tip my hat to DeCode," he said. "But the technology is now widely available," and, in his view, the only barrier to other teams contributing to gene discovery would be if they dropped the high standards of statistical rigor developed by the three academic consortia.

Several of the new variant genes make the pancreatic beta cells produce less insulin, Dr. Altshuler said. That suggests that diabetes may start as a disease of too little insulin production, even though patients turn up in the doctor's office making too much insulin, to which their tissues have become resistant.

The variant genes found so far account for only two to 20 percent of the overall risk of diabetes, implying there are many more to be found. The present genes are not sufficient to distinguish reliably between people at low- or high-risk for diabetes, Dr. Boehnke said.

By mapping the human genome, scientists are discovering which individuals are more prone to certain diseases and conditions. But genetics are just half the story - how you treat your body when you're young will also certainly affect your health when you get older.