The power of genomic medicine lies in the ability of the clinician to connect data from a person’s genomic test, laboratory results, and lifestyle to then recommend disease prevention or treatment strategies that are efficacious and truly personalized.
The case report below exemplifies the power and precision of genomic medicine.
James is a 48-year-old male. His father had died of a heart attack at age 50, and James was worried about his own health.
On the surface, James appeared healthy: 73 inches tall, 195 lbs, , and he exercised regularly at a fairly high intensity. He had been diagnosed a few years ago with intermittent hypertension that responded well to a very low dose of Lisinopril medication, but often he didn’t need to take it and wondered if he really needed it. His recent physical showed upper normal blood pressure of 138/80, and routine labs were normal, including Complete Blood Count, Lipid and Chemistry Profiles, and Hemoglobin A1C.
Using comprehensive genomic testing, we were able to look deeper beyond his signs and symptoms and identify predispositions to metabolic dysfunctions that increased his cardiovascular risk. Here are some highlights of his evaluation and the resulting DNA-directed roadmap created for him.
Apolipoprotein dysregulation in lipid metabolism is known to increase a person’s risk of cardiovascular disease. While functional medicine testing can evaluate many clinically important lipoproteins, it cannot evaluate all of them. A comprehensive cardiometabolic genomic test can examine whether the genes encoding for virtually all of the lipoproteins, not just APOE, are functional, marginally functional, or severely impaired. Stringing all that information together can give the clinician a more complete picture of how well all the lipoproteins associated with lipid metabolism are “playing” together, and, if not, then which evidenced-based interventions would establish or re-establish homeostasis.
James had only a few gene SNPs in his lipid metabolism pathway, including ApoA1, LPL, and CETP, and his APOE genotype did not increase his risk for cardiovascular disease. Based on his genomic test results, lipoprotein dysregulation was not a major contributing factor to his risk of cardiovascular disease. More importantly for James, his genomic test results revealed many other important findings that increased his risk for heart disease.
Understanding the mechanism behind his mild hypertension was an important goal for James. His genomic test results revealed SNPs in ACE, AGT, and MR genes associated with his renin-angiotensin system, in addition to genes in other systems, were all contributing to his mild hypertensive events. His inability to metabolize caffeine meant his three cups of coffee a day were also affecting his blood pressure and increasing his cardiovascular disease risk.
A pharmacogenomic assessment was performed to determine whether the hypertensive medication prescribed by his physician would lead to a drug-gene interaction, which could put him at higher risk for adverse side effects or identify that the Lisinopril was not an effective choice. Fortunately, there were no variants associated with the genes in James’ metabolic pathways for the drug prescribed by his physician. Had there been, we would have informed his physician, provided him a copy of James’ pharmacogenomic report, and suggested an alternative.
We also discovered a major contributor to the episodic nature of James’ hypertension—gene SNPs involved in his response to stress.
Based on James’ DNA map, he was predisposed to an exaggerated stress response with an overproduction of both cortisol and catecholamines (epinephrine and norepinephrine). In addition, his ability to metabolize excess catecholamines was impaired. One of the gene SNPs noted in his results was in the COMT gene, which encodes the enzyme responsible for degrading these catecholamines. Stress plays a key role in a person’s risk for hypertension and risk for a cardiovascular event.
Reducing or alleviating the stressors in his life has been and will continue to be a critical focal point for James as he better understands the relationships between chronic and acute stress, his elevated blood pressure and risk for a serious cardiovascular event.
His genomic testing also revealed an increased risk of post-traumatic stress disorder (PTSD) related to childhood trauma. This prompted him to explore deeper with his therapist the significance of the drama and trauma during his childhood and how they were continuing to impact his life. The data from his genomic test helped validate his life-long experiences of feeling in a perpetual state of fight or flight, and helped to frame his ongoing support needs.
With his diagnosis of hypertension, James clinically had one of the major variables associated with metabolic syndrome, a significant risk factor for heart disease. But his weight was not an issue, and because he showed no sign of diabetes or pre-diabetes, his primary care physician felt this was not an issue for him.
His genomic testing, however, revealed numerous gene SNPs associated with an abnormal insulin response and glucose dysregulation. This prompted the need for a two-hour glucose tolerance test, which revealed early evidence of an impaired insulin response and inadequate glucose metabolism.
With this information, James understood the rationale for significant dietary changes that would reduce his glucose load and the burden on his insulin response. As part of a cardiovascular prevention plan, a yearly 2-hour glucose tolerance test was instituted to help him stay on his dietary regimen and alert his primary care physician to any significant changes in glucose regulation.
Elevated homocysteine is recognized as an independent risk factor for cardiovascular disease. The primary pathways involved in homocysteine are the transmethylation and transsulfuration pathways. These pathways are critical to a host of important biological systems, including emotional health. James had numerous gene SNPs in these pathways, including MTHFR, MTR, MTRR, TCN2, and others, which were contributing an elevated homocysteine level of 12 ųmol/L. DNA-guided interventions were recommended to optimize these two metabolic pathways, resulting in lowering his homocysteine level to seven ųmol/L, and restoring balance to the other biological systems dependent on proper functioning of the transmethylation and transsulfuration cycles.
Inflammation and Oxidative Stress
Besides the variables mentioned above, an increased risk of heart attack and stroke is related to a person’s inflammatory response and level of oxidative stress, both of which are intimately intertwined through connection of the NFKB and Nrf2 pathways.
James had many gene SNPs associated with both his proinflammatory response and free radical quenching in both extracellular and intracellular antioxidant systems. In fact, his DNA map revealed that his current exercise regimen was likely contributing to his chronic inflammation and oxidative stress burden. The solution was to modify his exercise to better reflect his underlying genomic makeup, and to provide specific nutrigenomic strategies to support these pathways based on his unique DNA profile.
In addition to the gene SNPs affecting the B vitamins associated with homocysteine, his genomic testing revealed numerous other vulnerabilities in the absorption, transport, and metabolism of micronutrients. One of particular importance to cardiovascular disease is CoQ10. This nutrient can be obtained through food as well as produced by the body, but aging and stress leads to depletion.
Functional medicine testing showed James’CoQ10 levels to be adequate given the CoQ10 supplement he was already taking. But his genes told a different story.
CoQ10 (ubiquinone) is considered a pro-nutrient; it must be converted to ubiquinol, its active form, to fulfill its biological roles in the body. The enzyme responsible for this conversion is encoded by the NQO1 gene. Unfortunately, lab tests only evaluate the precursor form, ubiquinone, because ubiquinol is very unstable. For those with impairment in this conversion process, ubiquinone is not a good biomarker for ubiquinol levels in the body. Due to a gene SNP on the NQO1 gene, James’ ability to convert CoQ10 to ubiquinol was dramatically reduced. When he switched from CoQ10 to ubiquinol, his brain fog ceased, and his fatigue greatly improved.
Although ubiquinol is more expensive, James knew this had to be part of his daily regimen for life. From his DNA profile, we now knew that routine CoQ10 testing was not a good measurement for him, or an effective use of his resources.
With insights gleaned from the results of his comprehensive genomic testing and then integrated into a comprehensive health model, a personalized DNA-guided roadmap was created for James. This document outlined his priorities for dietary and lifestyle changes, as well as ongoing lab work that would be most beneficial and clinically relevant.
With this backdrop, we could personalize very specific interventions across emotional health and stress management, dietary changes, nutritional supplements, and exercise recommendations, restoring homeostasis to biochemical and metabolic systems not readily seen or felt by patients. In the process, we were also able to give James a more concrete understanding of an abstract phenomenon called genomic medicine.
It was very empowering for James to get answers about his health, and to understand how his DNA as well as dietary, environmental, and life experiences interact to influence his risk of hypertension and cardiovascular disease. His health and energy improved dramatically, and he no longer needs antihypertensive medication.
Just as important, James no longer has to guess what he needs to be healthy. He now has a blueprint and the tools to change his health destiny. He no longer fears that he will suffer the same fate as his father.
Personalized, DNA-directed healthcare saves time, energy, and resources for both the patient and the healthcare professional. This is the premise and promise of genomic medicine.