At least two "diabetes genes" predict the risk of Type 2 diabete

Nov 1 2005

Scandinavian researchers have confirmed that at least two "diabetes genes" predict the risk of Type 2 diabetes (T2D) when combined with lifestyle factors, in the largest study of its kind to date.

Scientists believe that such genetic risk factors might be used to design tests that, when assessed with lifestyle factors, such as obesity, will allow clinicians to predict an individual's risk of the disease.

According to the World Health Organization, 150 million people have diabetes, 90% of whom have Type 2 diabetes. T2D is a multifactorial disease in which environmental triggers, such as diet and obesity, interact with genetic variants to make up an individual's predisposition to the disease. The disease, mainly found in adults but increasingly common in children, is characterized by impaired insulin secretion and insulin action in tissues such as muscle and liver. Many patients with a genetic predisposition to T2D also have a tendency to gain weight.

Several gene variants have been associated with T2D, but knowledge of their predictive value has been hampered by the fact that few have been assessed in long, large-scale, prospective observational studies--until now. In this month's open access journal PLoS Medicine, scientists from Sweden and Finland tested several known candidate genes for T2D for their ability to predict diabetes in 2293 people without diabetes in the Botnia prospective study in Western Finland from 1990 to 2002. The team from Lund University, Malmo, Sweden found that "variants in the PPARG and CAPN10 genes increased the future risk for Type 2 diabetes, particularly in individuals with other risk factors."

One of the advantages of this study over previous ones, which looked for associations between gene mutations and T2D, is that in other studies, patients were usually gathered from diabetes clinics, which might have been biased towards patients with more severe genetic variants, said the authors.

"It was therefore encouraging to see that polymorphisms in some genes previously shown to be associated with T2D in case-control studies (particularly P12A in the PPARG and SNP44 in the CAPN10 genes) could predict T2D in high-risk individuals from families with T2D," they wrote.

One of the limitations of this study was that it still wasn't large enough to account for low frequency alleles--different variations of the same gene. These findings will need to be replicated in larger, prospective studies, such as the Malmo Diabetes Prevention cohort study, in which 22,000 individuals are being followed for more than 20 years.