With the incidence of type 2 diabetes increasing alarmingly, science is looking to genetics to better understand the processes underlying this chronic illness. A new study has isolated a gene not previously associated with diabetes that seems to lead to the pancreatic dysfunction that causes the disease.
The International Diabetes Federation (IDF) predicts that, by 2045, 12.2% of the world’s population will be living with diabetes. Type 2 diabetes (T2D) is the more prevalent form of the disease, accounting for around 90% of all cases of diabetes. In healthy people, pancreatic islet cells secrete insulin, specifically the pancreatic beta cells. In type 2 diabetics, the cells do not secrete enough insulin, and this, often coupled with insulin resistance, leads to chronic high blood glucose or hyperglycemia.
Previous studies have identified some of the genes responsible for T2D, but most involved relatively small sample sizes and lacked validity, which is the extent to which a study’s conclusions can be considered accurate and reliable. At the same time, genome-wide association studies, which uncover the genes associated with a particular disease, have identified hundreds of genetic signals associated with T2D, particularly affecting the beta cells’ ability to secrete insulin.
Researchers from Lund University studied the pancreatic islet cells of a large group of type 2 diabetics and non-diabetics using RNA sequencing, a process that determines which genes are switched off in a cell, how much DNA has been copied into an RNA molecule (transcription), and at what times the genes are activated or switched off.
The researchers found 395 differentially expressed genes (DEGs) in the islet cells of participants with T2D. A gene is called "differentially expressed" if an observable difference in expression levels between two experimental conditions is statistically significant.
Of the 395 DEGs found, only 94 of them were previously known. The DEGs were examined to see whether they predisposed people to T2D.
The overexpression of one particular gene, PAX5, was strongly associated with impaired insulin secretion by the beta cells. Whereas PAX5 was previously associated with leukemia, there had been no known connection between the gene and diabetes until now.
“One of the strengths of our new study is that we have been able to validate already known genes, at the same time as we have discovered many new genes that are differently expressed in individuals with type 2 diabetes,” said Professor Charlotte Ling, co-lead author on the study. “We have also been able to identify a gene that proved to be very strongly associated with impaired insulin secretion."
Now that PAX5 has been identified as a potential cause of T2D, further study will determine whether it is possible to fix the problem gene using CRISPR/Cas 9 gene editing technology.
“Our long-term goal is to regulate the activity of PAX5 using the [CRISPR] genetic scissors and that way restore PAX5 levels in individuals with type 2 diabetes,” Ling said.
The study was published in The Journal of Clinical Investigation.
Source: Lund University via EurekAlert!