A variation on a gene brings unexpected benefits

June 01, 2016

The variant of a gene encoding a drug target for a popular antidiabetic therapy is protective against heart disease, a common safety concern with antidiabetic medications, a new study shows. The study, which involved harnessing the genomic data of more than 50,000 people, suggests that drugs that target this gene are not necessarily associated with a greater risk of cardiovascular risk, as has been thought. Its authors say the results provides further support for the idea that genetics may offer a valuable tool for predicting a drug's possible side effects (or in this case, unforeseen benefits) earlier in the drug development process, promising to accelerate clinical testing and spare patients from potentially harmful medications. A drug's safety is rigorously tested in preclinical and clinical studies, but some side effects may not be discovered until after the drug goes to market and consumers report them. Turning to genomics for clues about drug-related risks, Robert Scott and colleagues combed through large-scale sequencing data on six different genes encoding proteins targeted by approved or experimental antidiabetic drugs. They uncovered a genetic variant of glucagon-like peptide-1 receptor (GLP1R), a receptor activated by current antidiabetic drugs to stimulate insulin secretion, that associated with lower risk of type 2 diabetes. The allele was not linked to a risk of coronary heart disease and in fact, appeared to reduce this risk, pointing to an unexpected benefit. Altogether, the findings highlight how studying genetic variants that mirror the effects of therapies targeting the same gene could help uncover side effects from those drugs. Ongoing clinical trials evaluating the cardiovascular safety of GLP1R-targeted treatments may add further insights into the study's findings.

American Association for the Advancement of Science

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