Population-specific trials and not common drug clinical trials for the entire world for any new medicine is important because of the presence of variant genes responsible for drug metabolism, say scientists of the CSIR-Centre for Cellular & Molecular Biology (CCMB) on Saturday.
Senior scientist K. Thangaraj, now director of the Centre for DNA Fingerprinting and Diagnostics (CDFD), and his team recently published the study of diversity of ‘CYP2C9’ gene or ‘Cytochrome-P450-2C9’ which is responsible for metabolism of a wide range of drugs, including anti-epileptic drug Phenytoin and anti-hypersensitive drug Losartan, in the journal ‘Pharmacogenomics and Personalized Medicine’.
CYP2C9 gene sequence changes may affect production of CYP2C9 protein in the human liver and this can cause slower metabolism of drugs like slower or a reduced rate of excretion of the drug. Such drugs have a narrow therapeutic index ,which means they are tolerated by our bodies in very specific amounts and when retained in the body for a longer period, can lead to toxicity.
Right dosage
Hence, it is important to decide the right dosage for each individual depending on the CYP2C9 gene sequence. This is also the reason why doctor-prescribed drugs fail to treat the disease and instead, lead to responses like rashes, vomiting, nausea or no response at all, sometimes. The blueprint of the proteins metabolising the drugs is in the genes of the person concerned and gene variations occur in a population.
Gene variation low
Yet, gene variation is less when the population is more endogamous such as in many communities of India. However, since the country has become a global destination for clinical trials of various drugs, it is important to study variants of genes for drug metabolism. “We found eight new variants of the CYP2C9 gene, making a total of 11 known variants in South Asia,” said Nizamuddin, first author in the study.
“CYP2C9 gene variations knowledge will help doctors decide on the right dosage of medicine for each patient and will also be vital for conducting meaningful clinical trials,” said Dr Thangaraj, the corresponding author.
No correlation
The study found no correlation between any of these variants with the linguistic and geographical population groups. But, a few Indian populations have more than 20% with a deleterious variant of CYP2C9 gene or ‘CYP2C9*3’ which reduces the ability to metabolise drugs. The eight new variants found in this study are also predicted to have a similar effect.
“Healthcare is now moving towards personalised medicine and our studies on genetic diversity of India will play a key role in this transition,” said CCMB director Rakesh Mishra.
