Faulty peptide behind disorders
doi:10.1038/nindia.2012.177 Published online 1 December 2012
Researchers have homed in on new genetic variations in a specific coding region of a gene that give rise to altered structure and activity of catestatin (CST), a peptide known to regulate levels of blood sugar, triglycerides and catecholamines. CST is synthesized from the gene that codes for the chromogranin A (CHGA) protein.
This new finding may help design genetic screening techniques to identify individuals at risk of developing CST-mediated cardiovascular and metabolic diseases long before clinical symptoms appear.
Patients with high blood pressure had lower blood levels of CST peptide, suggesting a protective role for this peptide against the development of hypertension. Although studies in Western populations have detected how genetic variations could alter the activity of CST peptide, no Indian studies have linked genetic variations to pathogenic roles of CST peptide.
In the hope of linking genetic variations to altered activity of CST peptide in Indians, the researchers analyzed blood samples to detect variations in the CST-coding region of the CHGA gene, and measured levels of glucose, catechlolamines and triglycerides in 1010 individuals selected from Chennai-based Madras Medical Mission Hospital.
The study detected two single nucleotide polymorphisms (SNPs), changes in a single base in the CST-coding region of the CHGA gene. One SNP led to replacement of the amino acid glycine by serine, and the other led to replacement of glycine by valine, leading to formation of two variant CST peptides.
Individuals carrying CST variants showed diminished blood levels of catecholamines with higher levels of glucose and triglycerides compared to individuals carrying normal CST.
"Besides the prospect of genetic screening, this finding may help develop new therapeutic agents to fight off diseases such as hypertension, diabetes and hyperlipidemia, in which CST has regulatory roles," says lead researcher Nitish R. Mahapatra.
The authors of this work are from: Department of Biotechnology, Indian Institute of Technology Madras, and Institute of Cardiovascular Diseases, Madras Medical Mission, Chennai, and Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
- Sahu, B. S. et al. Functional genetic variants of the catecholamine-release-inhibitory peptide catestatin in an Indian population: allele-specific effects on metabolic traits. J. Biol. Chem. doi: 10.1074/jbc.M112.407916 (2012)