Gene Signature Identified for Diabetes Prediction

Gene Signature Identified for Diabetes Prediction

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Highlights:
  • Gene signature which involves over 80 gene variations present in multiple genes has been identified.
  • The gene variations affects the binding of the regulatory factor X (RFX) which leads to an imbalance in the blood sugar
  • The gene signature may be used for personalized care for diabetics
Diabetes has always been a mystery to most scientists who have tried to understand why some people develop this disease while others don't. 80 small variations in the genes carried by people have been identified, while certain variations are associated with the increase in risk for this disease, other variations are found to protect people from the damaging effects of high blood sugar. This is the first study to identify " Type 2 diabetes ".
Gene Signature Identified for Diabetes Prediction

A research team has now discovered that variations in many genes could lead to the development of this disease. The variations in certain genes are found to alter the way the genes are read by the pancreas. The study was published in the journal Proceedings of the National Academy of Sciences and includes scientists from The University of North Carolina, National Institutes of Health, the University of Michigan, the University of Southern California and the Jackson Laboratory for Genomic Medicine.

Personalized Treatment for Diabetes

The identification of the gene signature could aid in providing personalized treatment for diabetes and to assess risk for the disease. The scientists have discovered that the binding of regulatory Factor X (RFX), which is found to be the master regulator of many genes, is affected. This is the first study that has shown that alterations in many DNA-associated genes are linked to the same DNA-reading molecule.

The findings of the study are that
  • Many variations in the genes associated with diabetes alter the ability of RFX to bind to certain regions of genomes of islets.
  • This affects the ability of these pancreatic cluster cells (islets) to perform their functions.
The islets are important for maintaining blood sugar levels of people as they secrete hormones like insulin and glucagon. Among diabetics, the blood sugar maintenance is affected which results in other associated health problems.

U-M Medical School's, Dr. Stephen C.J. Parker who is an assistant professor of computational medicine and bioinformatics said that the subtle changes in DNA could increase the risk for Type 2 diabetes which affects the common regulatory pathway among the islet cells. The RFX does not understand the variations in the gene which disrupts the regulatory pathway, paving the way for increased genetic risk for Type 2 diabetes.

Genetic Studies

The research team analyzed the DNA from islet samples of 112 people. They studied
  • Differences in DNA sequences
  • Epigenetic factors that include DNA packaging
  • Expression levels of genes
These would aid in identifying the translation pattern of genes. The "footprints" of RFX could be identified. The RFX was found to attach to a region just ahead of the gene associated with diabetes, a short length of DNA close to the gene.

The variations in the gene that have been associated with diabetes result in a disruption of this stretch of DNA, preventing the binding of RFX. Every change in the DNA results in changes in the way the RFX binds, which in turn affects the regulation of blood sugar in the body. The most significant factor is that there were changes in the area where RFX is believed to bind to that of the cells in the islets.

The study showed how alterations in the gene influence the epigenome or the factors that affect gene expression.

Mitchell-Riley Syndrome

The research team involved in the study believe that the Mitchell-Riley syndrome, a severe form of diabetes that occur in a small percentage of babies born every year may be associated with mutations in RFX. This condition, inclusive of neonatal diabetes, is characterized by the malformed pancreas, and caused by an autosomal recessive mutation found in certain forms of RFX.

Benefits of Using Gene Signature for Diabetes Prediction

There are many benefits associated with using biomarkers or gene signatures for prediction of diabetes.
  • They aid in learning about the disease pathways which can be used to limit the risk of complications associated with the disease like diabetic ketosis
  • Early detection can be used to prevent diabetes entirely.
  • Gene screening will limit the need for unnecessary biochemical tests
  • Interventional strategies can be adopted by people at high risk
The gene signature that has been identified for diabetes will aid in personalizing treatment and care. People who are highly prone to diabetes can now modulate their lifestyle factors to minimize risk.

References:
  1. Predicting Type 1 Diabetes Using Biomarkers - (http://care.diabetesjournals.org/content/38/6/989)
Source: Medindia

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