CCMB team identifies variants of genes that metabolise drugs – BusinessLine

As India emerges a destination of global choice for clinical trials of various drugs, a study on variants of the gene important for drug metabolism seeks to explore how drugs function across diverse populations.

Dr K Thangaraj and his team from CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, recently published their study of diversity of cytochrome-P450-2C9 (CYP2C9) gene in Pharmacogenomics and Personalized Medicine.

Healthcare is now moving towards personalised medicine. Our studies on the genetic diversity of India will play an important role in this transition, says Dr Rakesh Mishra, Director, CCMB.

The study is important as it seeks to analyse doctor-prescribed dose of drugs based on the gender, age and body mass index (BMI) of patients. However, there are hypersensitive response like rashes, vomiting and nausea.

Individuals in a population have variations in their genes needed for metabolism of a wide range of drugs. Any changes in the sequence of gene may affect the production of protein in human liver. This can cause slower metabolism of a drug and slower or reduced rate of excretion. Many of these drugs have a narrow therapeutic index they are tolerated by human bodies in very specific amounts, according to scientists.

When these drugs are retained in the body for longer, that can lead to toxicity. So, it is important to decide the right dosage for each individual depending on the sequence of their CYP2C9 gene.

Dr Thangarajs 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 other countries of South Asia. We found eight new variants of the CYP2C9 gene, making a total of 11 known variants of the gene in South Asia, says Dr Nizamuddin, who is the first author in the study.

They find no correlation between any of these variants with the linguistic and geographical population groups. However, a few Indian populations have more than 20 per cent people with a deleterious variant of the gene. 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, says Dr Thangaraj, the corresponding author of this paper and presently Director of the Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad.

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CCMB team identifies variants of genes that metabolise drugs - BusinessLine

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