Almost 26 million children and adults in the US have diabetes, while 79 million of us have pre-diabetes. Now, researchers have identified rare mutations in a gene that they say could prevent type 2 diabetes – the most common form of the disease – even in people who have risk factors for the condition.
The international research team, led by investigators from the Broad Institute of the Massachusetts Institute of Technology and Harvard, and the Massachusetts General Hospital, recently published the findings in the journal Nature Genetics.
The researchers say that if a drug can be created that mimics the protective effects of these mutations, this could open the doors to the prevention of type 2 diabetes.
To reach their findings, the investigators analyzed the genes of 150,000 individuals over five ancestry groups using next-generation sequencing.
All participants had severe risk factors for diabetes, including advanced age and obesity. However, none of the subjects had developed the condition and had normal blood sugar levels.
An initial analysis of individuals from Sweden and Finland revealed a mutation in a gene called SLC30A8 that stopped it from functioning – a discovery the research team found surprising. Previous studies in mice had shown that mutations in this gene increased the risk of type 2 diabetes.
Further analysis of subjects from Iceland led to the discovery of a second mutation in the SLC30A8 gene that also halted its function. This particular mutation reduced the risk of type 2 diabetes and decreased blood sugar in subjects without diabetes with no negative outcomes.
Most recently, the investigators set out to see whether these mutations discovered in the SLC30A8 gene could be found in a wider population, so assessed the genotypes of individuals from multiple ethnicities.
This led to the discovery of a further ten mutations in the SLC30A8 gene that reduced the risk of type 2 diabetes.
The research team combined all of the results to find that inheriting one copy of a mutated SLC30A8 gene reduced the risk of type 2 diabetes by 65%.
Further laboratory analysis revealed that the mutations found in SLC30A8 disrupt the normal function of ZnT8.
ZnT8 is a protein encoded by SLC30A8 that carries zinc into beta cells that produce insulin. Once zinc is in these beta cells, it plays an important part in insulin crystallization. But the researchers say they have yet to discover how a reduction in ZnT8 reduces the risk of type 2 diabetes.
Commenting on the findings, co-author Tim Rolph, vice president and chief scientific officer of Cardiovascular, Metabolic & Endocrine Disease Research at Pfizer Inc, says:
“Through this partnership, we have been able to identify genetic mutations related to loss of gene function, which are protective against type 2 diabetes.
Such genetic associations provide important new insights into the pathogenesis of diabetes, potentially leading to the discovery of drug targets, which may result in a novel medicine.”
Medical News Today recently reported on a study detailing the discovery of seven new genetic regions for type 2 diabetes.