The Role of Pharmacogenetics in Personalised Treatment

Even before SmartDNA came along, I have always been fascinated about genetics and medicine, since being introduced to it in Biology in school way back in the 80s, and it was in lots of sci-fi books I read as a youngster.

Hollie has a sister who has some genetic variations, so she's very fascinated by it too, so I suggested she write a research piece and this article is the result. So please, come in and discover the world of Pharmacogenetics and how this fairly new branch of science can improve your health.

Pharmacogenetics, often abbreviated as 'PGx', explores the role of the genome in drug response. It blends pharmacology (the study of drugs) with genetics (the study of genes and their functions) to understand why people react differently to the same medication. Each person's genetic makeup is unique, impacting how their body processes drugs, encompassing absorption, distribution, metabolism, and excretion (ADME).

Genetic Variants in Drug Metabolism

A primary focus of pharmacogenetics lies in identifying genetic variants that affect drug-metabolising enzymes, such as cytochrome P450 enzymes, which are pivotal in metabolising many medications. Variations in these enzymes can lead to differences in how drugs are broken down, affecting their efficacy and potential side effects.

For instance, some individuals possess genetic variants resulting in reduced activity of specific drug-metabolising enzymes. This reduced activity can cause medications to accumulate in the body at higher levels than expected, heightening the risk of adverse effects. Conversely, others may metabolise drugs too swiftly due to genetic variants, potentially diminishing the drug's effectiveness.

Genetic Variants and Allergy Responses

Another critical aspect of pharmacogenetics involves understanding genetic variations in drug targets—proteins or receptors in the body that medications interact with. Variants in these targets can influence how strongly a drug binds to its intended site, affecting its therapeutic effects. In relation to allergies and immunology, specific genetic variations have been linked to differential responses to allergens and medications.

HLA-DQ:

• Variants in the HLA-DQ genes are associated with susceptibility to conditions and certain drug allergies. Individuals with specific HLA-DQ variants may have a higher risk of developing an allergic reaction to certain medications or foods. For example, variations of the DQ2 and DQ8 alleles, such as one or two copies of each, can lead to an elevated risk of developing coeliac disease. Interestingly, HLA-DQ2 is most commonly found in individuals of northern and western European descent, and HLA-DQ8 is more prevalent in those of Latin American and Native American ancestry.

FCER1A:

• Variants in the FCER1A gene, which encodes the alpha chain of the high-affinity IgE receptor, are associated with differences in IgE levels. IgE stands for Immunoglobulin E. It is a type of antibody (or immunoglobulin) that plays a crucial role in the body's immune response, particularly in allergic reactions. Elevated IgE levels are a hallmark of allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis. Genetic variations in FCER1A can thus influence an individual's propensity to develop allergic reactions and their severity, such as itching, swelling, mucus production, and in severe cases, anaphylaxis.

Clinical Application of Pharmacogenetics

The application of pharmacogenetics in clinical practice holds significant promise for personalised medicine. Genetic tests can now identify specific genetic markers that predict how a patient will respond to certain drugs. This information empowers healthcare providers to customise treatment plans, selecting medications and doses that are most likely to be effective and safe for each individual. For instance, identifying a patient with a variant in the HLA-DQ gene can alert a healthcare provider to the heightened risk of certain drug allergies, leading to the selection of alternative therapies. Similarly, knowing a patient's FCER1A status can help in tailoring treatments for allergic conditions, potentially improving efficacy and reducing adverse effects.

Limitations & Barriers

However, several limitations temper the enthusiasm for its clinical application. One significant challenge is the complexity of genetic interactions. Drug responses are often influenced by multiple genes, making it difficult to predict outcomes based solely on single gene variants. Diseases, like cancer, HIV, type 2 diabetes, and Covid-19 can cause changes or mutations in DNA, impacting how our bodies react to medication, which can prevent PGx testing from painting a clear picture.

Moreover, many factors are not accounted for in standard pharmacogenetic testing. Age and environmental factors, such as pollutants and stress, are known to modify gene expression through epigenetic changes. Lifestyle choices, including diet and exercise, also impact gene expression and can cause epigenetic modifications. Nutrients such as folate (Vitamin B9), Vitamin B12, polyphenols, and sulforaphane are all known to play a role in DNA methylation and gene expression processes. These factors, which significantly influence drug response and efficacy, are typically not considered in standard pharmacogenetic testing, highlighting a critical limitation in the current approach.

Another critical limitation is the variability in genetic data across different populations. Most pharmacogenetic studies have been conducted on relatively small and homogeneous groups, predominantly white Europeans, which restricts the generalisability of their findings. This lack of diversity can lead to disparities in the applicability and accuracy of pharmacogenomic testing across different ethnic groups. Additionally, the high cost of pharmacogenomic testing remains a significant barrier to widespread implementation and accessibility, limiting its potential benefits to a broader population.

Our understanding of the genetic factors affecting drug response is still incomplete, and many genes involved in drug metabolism remain unidentified or poorly understood, and there are times where a patient’s results suggest they may metabolise one drug poorly, but they may respond very well to treatment, and vice versa.

Conclusion

Whilst there are limitations, PGx is still one tool that may be used in prescribing medication for various ailments and illnesses that may require medications such as ibuprofen and codeine, statins, antidepressants, antipsychotics, and antiepileptic medication.

Pharmacogenetics represents a critical advancement in healthcare, striving to optimise drug therapy through a personalised approach based on individual genetic profiles. As the field continues to evolve, it has the potential to change how medications are prescribed, ultimately enhancing patient care and outcomes. It provides physicians with a reliable guide for prescribing treatments, minimising the trial-and-error period, and can be effectively combined with other therapies, like nutrition, aromatherapy, mindfulness, and counselling, as part of a holistic approach to treating ailments.

If you are interested in gaining more insight into your unique genetic profile, you can order a smartDNA Genomic Wellness Test Plus, along with pre-test and post-test consultations to guide you through the process, and help you understand your results and what they mean for your healing journey.

  Remember, if you experience any of these symptoms, seek medical advice promptly.

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