Connecting the Clinical Dots Using Genomic Testing

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.

Meet James

James is a 48. 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. He ate a mostly plant-centered diet, 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 medication, but often he didn’t need to take it. At times he wondered if he really needed it. His recent physical showed upper normal blood pressure, and routine labs were normal. He was told all was good, and to come back in a year for his next checkup. But he wanted more.

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.

Lipid Metabolism

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. Genoma International’s genomic testing can examine whether the genes encoding for these lipoproteins, far more than just APOE, are potentially impacting lipid metabolism and cholesterol. 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, 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. But he was not in the clear – his genomic test results revealed many other important findings that increased his risk for heart disease.

Hypertension

Understanding the mechanism behind his mild hypertension was an important goal for James. His genomic test results revealed SNPs in genes associated with several systems, including his renin-angiotensin system, were contributing to his mild hypertensive events. A diet lower in sodium, and balancing other minerals, was important. 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.

Genoma International’s Pharmacogenomic test panel revealed that the medication he was taking was a good choice for him, and did not need to be changed.

All of this information was helpful, and then his genomic test results revealed something more: his biggest risk factor for heart disease, and an underlying cause of his hypertension, was linked to his stress response.

Stress Response

Based on James’ DNA map, he was predisposed to an exaggerated stress response with an overproduction of both cortisol and catecholamines. In addition, his ability to metabolize these catecholamines was impaired. When James saw his results, he understood that managing the stressors in his life needs to be a critical focal point to control his blood pressure and reduce his 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.

Metabolic Syndrome

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 he was slim, 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 a different story. He had numerous gene SNPs associated with an abnormal insulin response and glucose dysregulation, putting him at high risk for diabetes. 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 risk for diabetes, and why regular monitoring was needed.

Homocysteine

Elevated homocysteine is recognized as an independent risk factor for cardiovascular disease. James had numerous gene SNPs in these pathways, contributing an elevated homocysteine. DNA-guided interventions were recommended, resulting in lowering his homocysteine and restoring balance.

Inflammation and Oxidative Stress

In addition to 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. 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.

Micronutrients

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.

Lab 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. For those with impairment in this conversion process, ubiquinone is not a good biomarker for ubiquinol levels in the body. Unfortunately, lab tests only evaluate the precursor form, ubiquinone, because ubiquinol is very unstable. Only through knowing James’ DNA profile did he learn that the CoQ10 supplement he was taking was not an effective strategy for him. When he switched from CoQ10 to ubiquinol, his brain fog ceased, and his fatigue greatly improved.

A DNA-Directed Roadmap

Using the 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. It 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 interacted with dietary, environmental, and life experiences to influence his risk of hypertension and cardiovascular disease.

His health and energy have 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.