CCMB finds drug metabolism defect in people of some communities practising endogamy

Scientists from Centre for Cellular and Molecular Biology (CCMB) have found that more than 20 per cent people of some castes and communities in India practising endogamy have a harmful variant of the CYP2C9 gene that puts them at a disadvantage in tems of drug metabolism (the rate at which drugs are processed by the body) .

CYP2C9 is needed for metabolism of a wide range of drugs, including anti-epileptic drug phenytoin and anti-hypersensitive drug losartan. Any changes in the sequence of CYP2C9 gene may affect the production of the CYP2C9 protein in the human liver, This can slow the metabolism and thereby the drug’s therapeutic effect.

Many such drugs have a narrow therapeutic index, which means they are tolerated by human bodies only if they are in a very specific amount. When these drugs are retained in the body for longer, it can lead to toxicity.

Researchers state that deciding the right drug dosage for each individual based on their CYP2C9 gene sequence is thus vital.

Dr K Thangaraj and his team from CSIR-Centre for Cellular and Molecular Biology (CCMB) studied the diversity of cytochrome-P450-2C9 (CYP2C9) gene among 1,488 Indians across 36 population groups, representing different linguistic groups, castes and tribes among other parameters. The study included caste groups from Andhra Pradesh, Telangana and Karnataka.

CCMB researchers also analysed the genes of 1,087 individuals from other 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 Sheikh Nizamuddin, one of the study’s co-authors.

No correlation was found between any of these variants in the linguistic and geographical population groups.

However, a few Indian populations have more than 20 percent people with the deleterious variant known as CYP2C9*3. “People 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.”

“We found that CYP2C9*3 is more prevalent in communities where endogamous marriages occur more frequently,” Dr Thangaraj, presently the director of Hyderabad-based Centre for DNA Fingerprinting and Diagnostics (CDFD), told DH.

The study was recently published in the journal Pharmacogenomics and Personalized Medicine.

“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. The study restates the need of population-specific drug trials,” said Dr Thangaraj, the study’s corresponding author.

“Such studies on the genetic diversity in India would play an important role in the transition of our healthcare system towards personalised medicine,” said Dr Rakesh Mishra, Director, CCMB.