DEC 19, 2017 5:10 PM PST

Human Genetic Variability Impacts the Efficacy of Medicine

WRITTEN BY: Carmen Leitch

The genetic material we carry in our cells is unique to us, and the field of personalized medicine studies how those individual differences affect our health, and the therapeutics that we use. Now, scientists from the University of Copenhagen and the MRC Laboratory of Molecular Biology in Cambridge have assessed the genetic differences between individuals in an important class of receptors, GPCRs. Drugs frequently target those receptors, and they wanted to know how drug efficacy may change depending on changes in the GPCR gene. Their work was reported in Cell.

A small number of people carry mutations in the GPCR gene that don't cause problems, but probably render medications ineffective. / Image credit: Pixabay

“We estimate that an average of three percent of the population have receptors that contain mutations which can alter the effect of medicine,” noted the first author of the study, Alexander Hauser, a postdoctoral fellow at the Department of Drug Design and Pharmacology at the University of Copenhagen. 

People that carry these mutations still have functional receptors, but the mutations have a varying effect on how well drugs work. “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,” explained the senior author of the work, Madan Babu, from the MRC Lab of Molecular Biology in Cambridge.

For this research, the investigators utilized whole genome sequencing to assess mutations in human GPCRs. They used data from about 2,500 individuals included in the 1,000 Genomes project, in addition to exome data, assessing the portions of the genome that are transcribed into RNA, from 60,000 participants of the ExAC project. Structural data was then employed to reveal the mutations that were most likely to change how medicine would work.

“The three percent of the affected population is an average. For some important receptors, it is way more. For instance, the relevant mutations occur in 69 percent of people in the GLP1 receptor that is the target of diabetes medicine and in 86 percent of people in the CNR2 receptor that is used as a target for medicine to relieve nausea induced by chemotherapy. But of course, we cannot know every person's genome and so these are estimates based on the data sets available,” said Hauser.

The researchers used their data to find out how many people were spending money on drugs that probably were not having any effect. In the UK, it resulted in an economic burden of at least 14 million pounds, or around 19 million dollars annually, when taking people with mutations in important places in both copies of their GPCR gene into account.

“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,” said Hauser.

Learn more about how genetics can be used to tailor therapies to the individual in this video about pharmacogenomics, from Mayo Clinic.


Sources: AAAS/Eurekalert! Via University of Copenhagen, Cell

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
JAN 10, 2020
Genetics & Genomics
JAN 10, 2020
Making Bad Fat Turn Good
Researchers want to turn unhealthy white fat, which stores calories, to healthier brown or beige fat that burns calories....
JAN 19, 2020
Genetics & Genomics
JAN 19, 2020
Engineering Mosquitoes to Stop Dengue Virus Transmission
The dengue virus is transmitted by mosquitoes. It is found in over one hundred countries and threatens three billion people with a serious illness....
FEB 24, 2020
Genetics & Genomics
FEB 24, 2020
Circular RNAs May Play a Role in Psychiatric Disorders
The genome contains the sequences for many genes that code for proteins. There are also regions and chemical tags that help control the activation of genes....
FEB 25, 2020
Genetics & Genomics
FEB 25, 2020
Improving Gene Therapy With Plant-Based Relatives of Cholesterol
Cholesterol analogs give nanoparticles a shape that helps them get where they need to go....
MAR 23, 2020
Genetics & Genomics
MAR 23, 2020
Diagnosing Cancer by Looking for Microbial DNA in the Blood
Liquid biopsies aim to diagnose a disease with only a bit of biological fluid, usually blood....
APR 03, 2020
Genetics & Genomics
APR 03, 2020
Physical Forces Can Change How Genes Are Expressed
Less than a millisecond after a cell is stretched out, genes are activated, which will result in the production of proteins....
Loading Comments...