The effect of medicine can vary significantly from person to person due to distinct human DNA mutations. Every person has a unique DNA sequence, and a study published in the scientific journal Cell examines certain receptors known as GPCRs in human cells. These protein receptors are the primary targets of the largest group of marketed modern medicines.
How Human Mutations Alter the Effect of Medicine
By mining existing datasets, researchers have mapped the extent to which mutations occur within GPCR drug targets in individuals and studied what impact these mutations could have on the therapeutic effect of medicine.
“We estimate that an average of 3 percent of the population have receptors that contain mutations that can alter the effect of medicine,” says first author Alexander Hauser from the Department of Drug Design and Pharmacology at the University of Copenhagen.
“This might mean that the medicine simply works less efficiently. It can also mean that the medicine does not work at all, or causes adverse effects on patients,” adds Madan Babu from the MRC Lab of Molecular Biology in Cambridge, where Hauser conducted this research.
The Research Behind These Findings
The researchers analyzed mutations in human GPCRs using whole genome sequencing data from the 1,000 Genomes project with approximately 2,500 participants, as well as exome data from the ExAC project with over 60,000 participants. They then used structural data to identify critical sites in GPCRs to uncover which mutations are most likely to alter the effect of medicine on patients.
Which Receptors Show the Greatest Effect of Medicine Variation
The 3 percent figure represents an average across the population. For some important receptors, the impact on the effect of medicine is far greater:
- In the GLP1 receptor — a target of diabetes medicine — relevant mutations occur in 69 percent of people
- In the CNR2 receptor — used as a target for medicine to relieve nausea induced by chemotherapy — mutations occur in 86 percent of people
“But of course, we cannot know every person’s genome, and so these are estimates based on the datasets available,” says Alexander Hauser.
The Economic Cost of Altered Medicine Effects
The researchers used their findings alongside sales data for 279 GPCR relevant drugs from the National Health Service in the UK to estimate how much money is spent on medicine with little or no effect due to human mutations. As a conservative estimate, the economic burden on the UK National Health Service is at least £14 million annually, taking into account the number of people with mutations in both copies of the gene in important receptor target sites.
Personalized Medicine and the Future Effect of Medicine Research
“The prevalence and potential impact of variation in drug response between individuals is a strong argument for further researching this field. It also constitutes a fine example of why personalized medicine might be the way forward, even when we are talking about common drugs,” says Hauser.
Understanding how human mutations alter the effect of medicine is a core reason why diverse participation in clinical trials matters. When study populations reflect the full range of human genetic variation, researchers can better identify how individual differences affect drug response across communities. At FOMAT, our commitment to inclusive clinical research ensures that participants from all backgrounds contribute to findings that lead to more effective and personalized treatments for everyone. If you are interested in contributing to this kind of research, visit our active studies page to learn more about current clinical trials enrolling now.