Lurking diabetic gene identified
doi:10.1038/nindia.2013.6 Published online 17 January 2013
New research has zeroed in on genetic variations in a gene that codes for tumour necrosis factor (TNF)-alpha, a proinflammatory protein molecule known to trigger a chain of molecular events that lead to mass death of insulin-secreting beta cells in the pancreas1. Such genetic variations increase the risk of type 2 diabetes in normal individuals and those with mildly elevated blood glucose levels.
This finding raises the possibility of genetic screening techniques to detect such genetic variations and thereby predict the risk of type 2 diabetes.
People with mildly increased blood glucose levels are defined as individuals with prediabetes (IPD). Although not all IPD develop type 2 diabetes, some do. However, no studies have investigated the underlying genetic factors that may increase the risk of diabetes in IPD in any Indian populations.
In the hope of identifying genetic variations in IPD that could lead to diabetes, the researchers measured blood glucose levels in 122 IPD and 100 normal individuals attending various health camps and diabetic clinics in Kolkata.
They also probed the genomic DNA of peripheral blood mononuclear cells isolated from IPD and normal individuals. They identified single nucleotide polymorphisms (SNPs), changes in a single base, in genes for TNF-alpha and IL-6, proteins known to disrupt the insulin signalling process and pave the way for beta cell death.
The study found elevated levels of TNF-alpha due to genetic variations in the TNF-alpha gene in IPD. Among the genetic variations, the variation known as TNF-alpha-238AA/GA significantly contributed to increased levels of TNF-alpha.
"Even after modifying lifestyle factors, some of the IPD carrying the detected genetic variations in TNF-alpha gene progressed to diabetes," says Deep Dutta, one of the researchers.
The authors of this work are from: Department of Endocrinology & Metabolism, IPGMER & SSKM Hospital, and Department of Biochemistry, Dr. B.C. Roy Post-graduate Institute of Basic Medical Education and Research, IPGMER, Kolkata, India.
- Dutta, D. et al. Tumor necrosis factor alpha S238G/A (rs 361525) gene polymorphism predicts progression to type-2 diabetes in an Eastern Indian population with prediabetes. Diabetes. Res. Clin. Pract. doi: 10.1016/j.diabres.2012.12.007 (2013)