SNPs Associated with Gene-Drug Interactions in Hypertension Identified

Mutations in ADD2 are related to different reactions to beta-blockers, diuretics, and RAAS inhibitors.

A team of researchers believe that they have pinpointed a number of gene-drug interactions that could allow hypertension medication to be tailored to individual patients based on their genetics.

The investigators studied siblings with hypertension participating in a Genetic Epidemiology Network of Arteriopathy study. They took blood pressure readings and detailed the subjects’ drug regimens. They found a set of SNPs on the adducin 2 (ADD2) gene that may influence the regulation of blood pressure among people with hypertension.

“We suspected that ADD2 could be associated with differences in response to different antihypertensives because adducins have been proposed to regulate renal tubular transport of Na+ reabsorption and the development of hypertension,” says Sharon Kardia, Ph.D., associate professor, epidemiology and director, public health genetics program at the University of Michigan.

In the initial observations, variation in blood pressure was affected by genotype, drugs, and interactions between the two, according to the researcers. They then used cross-validation methods to test the predictive power of their findings on individuals outside the study group.

The scientists report that three SNPs were associated with differential blood pressure responses in beta-blocker users versus diuretic users, while two other SNPs were linked to differential responses in renin-angiotensin-aldosterone system inhibitor users versus diuretic users.

The researchers also say that the results provide initial evidence that the effects of genetic variation on blood pressure in people with untreated hypertension may be very different compared with those taking medication.

The study was performed by scientists from the University of Michigan, the University of Texas, Houston, and the Mayo Clinic. Results are published in BMC Medical Genetics.