Change in sequence of gene can affect production of CYP2C9 protein in human liver
Hyderabad: With India being a global destination for clinical trials of various drugs, scientists from the Centre for Cellular and Molecular Biology (CCMB), who studied the relationship between variants of genes and their role in drug metabolism, have found that diversity of a particular gene plays a role in how the human body processes drugs.
A study on diversity of cytochrome-P450-2C9 (CYP2C9) gene, published in the journal Pharmacogenomics and Personalized Medicine by Dr K. Thangaraj and his team from the CCMB, found that any changes in the sequence of gene may affect the production of CYP2C9 protein in human liver.
The study found that changes in the gene can cause slower metabolism of drugs slower or a reduced rate of excretion of the drug.
“Many of these drugs have a narrow therapeutic index — they are tolerated by our bodies in very specific amounts. When these drugs are retained in the body for longer, it can lead to toxicity. So, it is important to decide the right dosage for each individual depending on the sequence of their CYP2C9 gene,” the CCMB said in a news release about the study.
Dr Thangaraj’s team studied the diversity of this gene among 1,488 Indians across 36 population groups, representing different linguistic groups, castes and tribes among other parameters. They also looked into genes of 1,087 individuals from South Asian countries. “We found eight new variants of the CYP2C9 gene, making a total of 11 known variants of the gene in South Asia,” said Dr Nizamuddin who is the first author in the study.
The researchers found that a few Indian populations have more than 20 per cent people with a deleterious variant of the CYP2C9 gene and said that those with this variant are at a disadvantage in their ability to metabolise drugs.
The eight new variants found in this study are also predicted to have similar effect on drug metabolism.
“It is important to know the variations in the CYP2C9 gene to help medical practitioners decide the right dosage of medicine for each patient. The knowledge of this variation will also be important for conducting more meaningful clinical trials. This study also suggests that it might not be the best thing to conduct a common clinical trial for the entire world. We need population-specific trials,” according to Dr Thangaraj, the corresponding author of this paper and presently Director of the Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad.
“The healthcare is now moving towards personalized medicine. Our studies on the genetic diversity of India, will play important role in this transition, says Dr Rakesh Mishra, Director, CCMB.
