Scientists Identify New Diabetes Genes

Researchers from the Broad Institute of Harvard and MIT, Lund University in Sweden and the pharmaceutical company Novartis claim that they have made a key breakthrough in the battle against diabetes by mapping the significant clusters of new gene variants that raise the risk of Type 2 diabetes, the most common, obesity-linked form of the disease.

The findings by three international research teams and another team led by Dr. Kari Stefansson, CEO of deCODE Genetics, published on Thursday in the journals Science and Nature Genetics, respectively, offer novel insights into the biology of a disease that affects 200 million people worldwide.

The findings, presented in three reports by university scientists and one by a private company, bring the number of well-attested genes involved in adult-onset, or Type 2 diabetes up to 10, from the 3 known previously.

"This achievement represents a major milestone in our battle against diabetes. It will accelerate efforts to understand the genetic risk factors for this disease, as well as explore how these genetic factors interact with each other and with lifestyle factors," said National Institutes of Health (NIH) Director Elias A. Zerhouni, M.D.

The scientists said that the four newly identified genes, called CDKN2A, CDKN2B-both lying on chromosome 9, and IGF2BP2- on chromosome 3 and CDKAL1, come in two versions, and each high-risk version increased the risk of Type 2 diabetes by between 10 to 20 per cent. One of these new genes is linked to an increased risk of developing the disease, said the researchers.

"The genes that have been found here are, without exception, totally surprising," said David Altshuler of the Broad Institute of Harvard University and the Massachusetts Institute of Technology, who led another team.

The researchers also confirmed previous findings that associated six other genetic variants with increased diabetes risk. The genetic variants associated with diabetes that were confidently confirmed by the new research are, TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11 and FTO.

The scientists scanned the DNA of more than 32,500 people in five countries including Britain, Finland, Poland, Sweden and the U.S. to pin down spots that harbor genetic risk factors for this complicated killer. They tested the DNA of those people to find patterns of small gene variations known as SNPs more common in diabetics.

All the new findings are based on a new research technique called genome-wide association studies, in which scientists compare genetic samples from thousands of individuals with a specific ailment to those without it. Differences between the two are examined as possible genetic causes of the disease.

The newly discovered genes do not immediately suggest any new therapy, but scientists hope they may point to a new biological basis for the disease, from which effective treatments could emerge in time.

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia (high blood sugar). The World Health Organization (WHO) recognizes two main forms of diabetes: type 1 and type 2.

Type 1 is usually due to autoimmune destruction of the pancreatic beta cells which produce insulin, while Type 2 is characterized by tissue-wide insulin resistance and varies widely. It sometimes progresses to loss of beta cell function.

Types 1 and 2 are incurable chronic conditions, but have been treatable since insulin became medically available in 1921. Diabetes can cause many complications. Serious long-term complications include cardiovascular disease, chronic renal failure, retinal damage, nerve damage and erectile dysfunction.

Type 2 diabetes harms the body's ability to control blood sugar and can lead to heart disease, blindness and early death. With the most common form of diabetes the body gradually loses its ability to use insulin, a hormone key for turning blood sugar into insulin.

In United States, more than 20 million people now have type 2 diabetes and scientists estimate that about 54 million more are at risk of getting the illness. Diabetes is expected to affect 350 million people by 2025.

Obesity and lack of exercise are the major risk factors, but some previous studies linked the disease to heredity too. People with an affected parent or sibling are at 3.5 times greater risk of developing the disease than people from diabetes-free families.