Our Blogs

Where Pharmacogenomics Happens: A Tour of the Body’s Genetic Hotspots

Pharmacogenomics (PGx) offers a transformative approach to personalized medicine, enabling clinicians to tailor medication selection and dosing based on a patient’s genetic profile. Genetic "hotspots" have been identified as specific locations in the body where genetic variations frequently occur and influence drug metabolism. These hotspots are found throughout the body, playing important roles in the liver, kidneys, and brain.

The Liver and Drug Metabolism

The liver is the primary organ responsible for drug metabolism, largely due to the activity of the cytochrome P450 (CYP450) enzyme family. Variants in CYP450 genes, particularly CYP2C19, CYP2D6, and CYP3A5, profoundly affect drug processing. For example, CYP2C19 poor metabolizers are unable to adequately activate prodrugs like clopidogrel. This causes insufficient platelet inhibition, increasing the risk of cardiovascular events.

Similarly, CYP3A5 gene variants greatly influence the metabolism of immunosuppressants like tacrolimus. Individuals who are normal or intermediate metabolizers typically require higher doses to achieve therapeutic levels. Dosing based on one’s genotype helps these patients reach target drug concentrations more quickly, which may reduce the risk of organ rejection. This underscores the value of PGx in hepatology and transplant medicine.

The Kidneys and Drug Clearance

While the kidneys play a minimal role in drug metabolism, they are central to drug excretion. Genetic variants in renal transport proteins significantly impact how drugs are eliminated from the body. For instance, ABCB1 influences renal blood flow as well as glomerular filtration rate, with variations in this gene being associated with altered renal function.

The SLC22A2 gene influences the renal clearance of substances like creatinine as well as drugs such as digoxin and metformin. Alterations in these genes can lead to elevated plasma drug levels, increasing the likelihood of adverse effects.

Pharmacogenomic testing that includes kidney-specific genetic hotspots can help predict which patients are at risk for drug accumulation and toxicity, particularly when using renally excreted medications.

The Brain and Drug Sensitivity

The brain presents another area where genetic variability significantly shapes drug response. Approximately 85% of antidepressants are metabolised by the CYP2D6 gene. This gene also regulates the metabolism of other psychotropic drugs, including opioids. Poor metabolizers may experience inadequate pain control from codeine, while ultrarapid metabolizers have a high risk for opioid toxicity due to excessive morphine conversion.

Additionally, genetic variants in OPRM1 and DRD2 influence opioid receptor function and dopaminergic signaling, respectively. These genes can determine both therapeutic efficacy and the risk of side effects in psychiatric and pain management settings.

Genetic variability greatly impacts outcomes for psychiatric disorders, making it an important consideration when tailoring treatments for psychiatric disorders and chronic pain.

There are also genes, like APOE and BDNF that influence rates of brain development and atrophy. BDNF supports the growth and maintenance of neurons, which plays a key role in learning, memory, and cognitive performance. One of the common variants in this gene has been linked to changes in brain structure, reduced neuroplasticity, and a higher risk for psychiatric disorders.

Summary

Pharmacogenomics is reshaping clinical practice by integrating genetic insights into medication management. Genetic hotspots crucially dictate how drugs are metabolized, excreted, and how they act at their target sites, especially in the liver, kidneys, and brain. As our understanding of these gene-drug interactions deepens, the potential to enhance therapeutic precision grows.

Scylex Labs' PGx panels provide a powerful tool for healthcare professionals aiming to personalize therapy, reduce adverse drug reactions, and optimize treatment efficacy. Incorporating pharmacogenomic testing into routine care can elevate treatment from a generalized approach to one that is truly individualized.

Written By:

Vanessa Imus, MS, RDN,

Owner of Integrated Nutrition for Weight Loss

https://inutritioncenter.com/about/