SNP Genotyping in Pharmacogenetics: Customized Solutions for Biotechnology and Healthcare R&D
- Base Científica
- Oct 23
- 4 min read
Discover how SNP genotyping is revolutionizing personalized medicine. In the context of biotechnology and healthcare research and development (R&D), SNP genotyping is emerging as an essential technique for understanding genetic variations that affect drug response. This type of analysis is a specialized branch of pharmacogenetics (or pharmacogenomics) and can generate biomarkers that predict therapeutic efficacy and safety. In this comprehensive guide, we'll explore the fundamentals, methods, applications, and how your institution can implement these solutions for laboratories, biotechs, and universities seeking innovation in clinical and genetic research.
1. FUNDAMENTAL CONCEPTS OF SNPS AND PHARMACOGENETICS
1.1 What is an SNP?
A SNP (single nucleotide polymorphism) is a point variation in DNA between individuals; for example, a nucleotide "C" may be replaced by "T" at a specific position. When such variants occur with reasonable frequency in a population (e.g., >1%), they are considered SNPs and not merely rare mutations.
1.2 Relationship between SNPs and Pharmacogenetics
In pharmacogenetics, we seek to associate genetic variants (SNPs) with differences in drug absorption, metabolism, action, or elimination. These variants can alter drug-metabolizing enzymes, transporters, or targets, influencing efficacy, toxicity, or plasma levels.
Practical Examples in the Clinic:
SNPs in the CYP2D6 gene may modulate the metabolism of antidepressants (such as paroxetine) and antipsychotics
Variable values of TPMT enzyme activity associated with SNPs influence the risk of hematologic toxicity in treatments with thiopurines.
Patients with HIV need to analyze several polymorphisms to reduce side effects, especially the HLA*B27:01 allele, to determine whether or not to recommend the drug abacavir, as it can cause neurotoxicity to the individual.
2. SNPS GENOTYPING METHODS: CHOOSING THE IDEAL TECHNOLOGY
2.1 Classical Methods
PCR + RFLP (Restriction Fragment Length Polymorphism): amplifies the region containing the SNP using the PCR technique and then subjects this product to enzymatic digestion that differentiates alleles.
Sanger sequencing (or chain termination methods) : Amplifies the region through PCR and then reads the base at the SNP site directly.
These methods are ideal for validating individual SNPs, but have limitations for large-scale panels.
2.2 Large-Scale/Multiplex Methods
Microarrays or DNA chips (genotyping thousands of SNPs simultaneously)
Next Generation Sequencing (NGS) applied to panels or target regions
qPCR with specific probes (Hydrolysis)
These methods allow high throughput and are frequently used in R&D projects or clinical research.
2.3 Technology Comparison
Method | Advantages | Limitations | Best Application |
PCR + RFLP | Cheap, simple, applicable to isolated SNP | Not very scalable, requires a specific enzyme | Punctual validation |
Classical sequencing | Direct and reliable reading | Relatively high cost per sample | Diagnostic confirmation |
Microarrays / chips | High SNP density, scalable | Initial costs, infrastructure requirements | Population studies |
qPCR / TaqMan | Speed, sensitivity, applicable to medium panels | Limited to the number of probes available | Clinical routine |
3. PRACTICAL APPLICATIONS IN PHARMACOGENETICS: FROM THE LABORATORY TO THE CLINIC
3.1 Custom Dose Adjustment
If a patient is identified as a "poor metabolizer" for a given drug (e.g., via a CYP2D6 SNP), the standard dose can be reduced to avoid toxicity. An "ultra-rapid" metabolizer may require a higher dose or the use of alternative drugs. This approach significantly reduces adverse drug reactions and improves therapeutic efficacy.
3.2 Selection of Alternative Treatment or Drug
In oncology and psychiatry, some medications are metabolized by polymorphic enzymes: knowing the genotype can guide the choice of a drug with a lower risk of therapeutic failure or side effects. For example, in the use of antidepressants, CYP2D6 genotyping can help distinguish the best option between paroxetine and other alternative drugs. Personalized medicine has also advanced significantly in oncology, with techniques such as the use of patient-derived tumor organoids allowing for individualized testing of treatment response.
Another example is genetic variants in the DPYD gene that can lead to enzymes with reduced or absent activity. Individuals who have at least one copy of a nonfunctional DPYD variant (e.g., c.1905+1G>A (formerly 2A; rs3918290) or c.1679T>G (p.I560S; formerly 13; rs55886062)) will not be able to metabolize fluorouracil at normal rates. Consequently, these individuals are at risk for potentially fatal fluorouracil toxicity, such as bone marrow suppression and gastrointestinal toxicity.
3.3 Clinical Studies and Biomarkers
In clinical research projects or drug R&D, SNPs can serve as biomarkers for stratification or response prediction. This allows for more refined trial designs (e.g., including only individuals with a certain genotype), significantly increasing the chance of success and saving resources. Proper interpretation of test results is essential to extract maximum value from pharmacogenetic data and apply it effectively in the development of personalized therapies.
4. PRACTICAL EXAMPLE: CYP2D6 GENOTYPE STUDY IN PSYCHIATRY
A study conducted at USP examined CYP2D6 genotyping in patients taking paroxetine. Researchers found different metabolizer profiles (PM, IM, EM, UM), with 8.5% being PMs and 3.0% UMs. Patients with only one functional allele had higher plasma concentrations than those with two functional alleles.
This case demonstrates the direct impact of pharmacogenetics on clinical practice: this type of evidence illustrates how genetics can guide dose adjustments or therapeutic choices in clinical research and practical application in the laboratory.
IMPLEMENTATION IN YOUR LABORATORY
Customized Genotyping Solutions
Our team of experts is ready to develop custom SNP panels, from study design to results analysis.
Feasibility analysis
Detailed technical proposal
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References
Abacavir Therapy and HLA-B*57:01 Genotype. DEAN, L. In: Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012. Available at: https://www.ncbi.nlm.nih.gov/books/NBK315783/
Capecitabine Therapy and DPYD Genotype. DEAN, L.; KANE, M. In: Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2016. Available at: https://www.ncbi.nlm.nih.gov/books/NBK385155/
Effectiveness and safety of drugs and SNPs: a review article. MATOS, LEO; SANTOS, KEP Research, Society and Development , v. 11, n. 11, 2022. DOI: http://dx.doi.org/10.33448/rsd-v11i11.33628
Study of CYP2D6 gene polymorphisms and therapeutic response to paroxetine. PRADO, CM 2016. Thesis (Doctorate in Sciences) – School of Medicine, University of São Paulo, São Paulo, 2016. Available at: https://www.teses.usp.br/teses/disponiveis/5/5142/tde-06062016-113945/publico/PradoCM2.pdf
Pharmacogenetics / Pharmacogenomics [review]. NETO, MJR. Digital Repository of Fernando Pessoa University . Available at: https://bdigital.ufp.pt/entities/publication/7fd82c71-735c-4ddd-80c2-916df172a97b
PHARMACOGENETICS: Fundamentals and applications. HIRANO, LQL Seminar presented at the Federal University of Goiás, 2011. Available at: https://files.cercomp.ufg.br/weby/up/67/o/semi2011_Liria_Queiroz_2c.pdf
HLA-B*5701 screening for hypersensitivity to abacavir. MALLAL, S.; PHILLIPS, E.; CAROSI, G.; MOLINA, JM et al. The New England Journal of Medicine , vol. 358, no. 6, p. 568-579, 2008. Available at: https://pubmed.ncbi.nlm.nih.gov/18256392/
Pharmacogenetic implications of endothelial nitric oxide synthase (eNOS) in the use of phosphodiesterase-5 inhibitors. SILVA, PS; LACCHINI, R.; GOMES, VA; TANUS-SANTOS, JE. Brazilian Archives of Cardiology [online]. Available at: https://www.scielo.br/j/abc/a/MfzV7JxssdJtZjWwH6ctMXP/?format=html&lang=pt
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