Research carried out at the Hebrew University of Jerusalem has provided the first proof of molecular risk factors leading to type 2 diabetes, providing an "early warning" sign that could lead to new approaches to treating this and other human disease conditions.
Despite extensive research on the molecular basis for the variance in susceptibility between individuals to common diseases, the subject is still poorly understood. A prime example of this is type 2 diabetes (T2D), a very widespread human disorder.
What is it that characterizes the susceptibility to this disease? Epigenetic variations - which are small molecular marks superimposed on the DNA structure - have been frequently hypothesized to modify predisposition, but direct evidence was missing.
Now, a research team led by Dr. Asaf Hellman of the Hebrew University's Institute of Medical Research Israel Canada has developed a novel, multistep, study design involving the analysis of disease-contributing epigenetic variations among hundreds of patients and control individuals. The research was presented in a scientific conference at the Cambridge University Genomic Center and was recently published in the scientific journal Human Molecular Genetics
Taking an innovative research direction, the Hebrew University research team decided to map DNA methylation variations rather than DNA sequence variations, as was traditionally done. The team undertook a proof-of-concept study among 1,169 type 2 diabetes patients and non-diabetic controls. The results demonstrated the unique abilities of this novel research approach by revealing a clear-cut, disease-predisposing DNA methylation signature. This is a first report in the scientific literature of epigenetic risk factor for T2D.
DNA methylation is a naturally occurring mechanism used to regulate genes and protect DNA from some types of cleavage. It is one of the regulatory processes that are referred to as epigenetic, in which an alteration in gene expression occurs without a change in the nucleotide sequence of the DNA. Defects in this process cause several types of disease that afflict humans.
The method used by Hellman was developed during postdoctoral training at the Harvard University Medical School. Later, his research students at the Hebrew University, Gidon Tperoff and Dvir Aran, further developed it into an efficient, genome-wide mapping method.