Tips for Healthy Living: Eat Healthy, Exercise, and…Spit in a Tube

By Michael Lim

22 July 2019

We have all heard about the dangers of hypertension (HT) and cardiovascular disease (CVD), and the importance of a healthy diet and physical activity in warding off these potentially deadly conditions. Now, new research by Prof. Philip Millar shows that health-minded individuals may need to add another item to their checklist: examining their genes.

When you’re told stories about HT and CVD, you may simply think to yourself “that’s too bad” or “I hope that doesn’t happen to me”. But what Millar took away from these stories was an interest in the occurrence of HT and CVD.

“It’s a common story,” says Millar, a cardiovascular physiologist from the Department of Human Health and Nutritional Sciences. “Someone in your family is diagnosed with hypertension, and that makes you curious about why it occurs and how to treat it.”

Thanks to the growing popularity of genetic testing companies and decades of inheritance studies, it is widely known that HT and CVD can run in the family. Just like genes for traits such as hair colour, you can also inherit genes from your parents that are associated with increased health risks like CVD. But as the saying goes, “forewarned is forearmed”, and by knowing what genes you carry, you can better predict your chances of getting certain diseases and make changes to your lifestyle accordingly.

However, sometimes there can be multiple genes associated with a trait such as CVD risk that may influence each other to increase or decrease the expression of that trait. This can make predicting a person’s risk much more difficult. In these scenarios, researchers will sometimes focus on related genetic markers that can be used as a proxy.

This is what drove Millar’s focus on something known as the “exercise pressor response” (EPR). The EPR is how much an individual’s blood pressure changes when their muscles are engaged in exercise. Previous studies have shown this is an important measurement, as when the change in blood pressure is large, the individual is more likely to develop HT and/or CVD in the future.

As the physiological systems that control blood pressure during exercise are simpler than those that regulate it at rest, Millar suspected that the EPR could be the key to finding a genetic marker for HT and CVD risk. The trick, then, was to determine which genes (and their variants) are associated with differences in the EPR. 

Millar zeroed in one group of genes in particular, those that code for “metabolically sensitive receptors”. These are nerve endings often found in skeletal muscle, sending signals to the brain to control heart rate and blood pressure responses during exercise. By looking at past studies, Millar identified five sensitive receptors commonly involved in the EPR, including the ASIC3 (senses acidity), TRPV1 (senses acidity, heat, and pain), and BDKRB2 (involved in muscle contraction).

To find out if variations in the genes for these receptors were linked to differences in EPRs, Millar joined forces with Prof. David Mutch, a colleague in the Department of Human Health and Nutritional Sciences and expert in genomic analyses. The pair launched a study (led by MSc student Karambir Notay) that measured EPR in 200 healthy young men and women performing static handgrip exercises. Participants were also asked to conduct mental exercises (timed mental math questions), which served as a non-physical control to elevate blood pressure. Participants then provided blood or saliva samples so that their genome could be screened for common gene variants of the five metabolically sensitive receptors.

By comparing the participants’ gene sequences and their EPRs, the research team was able to identify gene variants for the TRPV1 and BDKRB2 receptors that had significant effects on blood pressure during exercise but not during mental tests. They also found that if both gene variants were possessed by an individual, the effect on EPR was even greater. Together, these results show exciting promise for TRPV1 and BDKRB2 gene variants as novel markers for HT and CVD risk.

Interestingly, the effects of these gene variants were especially strong in men. Millar believes the reduced effect in women may be attributed to high levels of estrogen, a female sex hormone, which appears to have a dampening effect on sympathetic activation, reducing EPRs.

To address the gender difference, future studies will involve older participants (such as women who are beyond menopause). Millar also hopes to include participants of different ethnic or geographic backgrounds to see if the effects observed in the study apply more widely to the general population. And Millar’s plans don’t stop there.

“In addition to providing a potential genetic marker for HT and CD, this research will hopefully answer of some of the field’s big picture questions,” says Millar. “For example, we know that interventions like exercise training can help increase cardiovascular health, but can exercise training help ameliorate the effects of these gene variants? We’ve only started taking our first steps.”

Funding for this research came from the University of Guelph-Humber Research Fund, the Ontario Ministry of Research, Innovation, and Science, the Ontario Ministry of Agriculture, Food, and Rural Affairs, the Canada Foundation for Innovation, and the Natural Sciences and Engineering Research Council of Canada.  

Read the full article in the Journal of Physiology.

Read about other CBS Research Highlights.