Pharmacogenomics

We are all genetically diverse and so is our response to medicines. In our body, medicines are metabolized through internal cellular pathways. Certain genetic variations (single nucleotide polymorphisms) are responsible for modifying these pathways and thereby impacting how our body responds to a specific drug.

GENOMIST helps you know which drugs will be impacted by your genetic makeup

GENOMIST helps in choosing the right drug based on these parameters:

• Toxicity/Adverse Drug Response:
  Certain genetic changes in the gene might lead to slow take up of the drug which in turn leads to excessive drug in the bloodstream. This can lead to adverse drug reaction or toxicity. Through GENOMIST testing, you can understand if you are at risk to have adverse reactions to certain drugs and avoid their use or use an alternative accordingly.
• Dosage:
  Your genetic report might help to decide the correct dosage for certain drugs and will save time in trial and error in figuring out the right dose
• Efficacy:
  GENOMIST report guides in knowing which drug might not work optimally on your body and your clinician may suggest an alternative therapy/drug

Our genetic makeup can either affect what the body does to the drug (pharmacokinetics) which includes absorption, distribution, metabolism and excretion or what the drug does to the body (pharmacodynamics) which includes drug receptor binding, efficacy and potency.

For eg:
Based on certain variants in this gene, there are five metabolizer phenotypes where drug activity would be as follows-

• Ultrarapid, rapid metabolizer – more than normal
• Normal
• Intermediate metabolizer – less active than normal
• Poor metabolizer – least activity

This would mean that in a few individuals the enzyme would break down some drugs quicker/ slower than the rest based on the metabolizer status. When people in these groups take normal doses of medicines, they may not see the wanted effect of the drug, experiencing either treatment failure or side effects. This would require the person to adjust the dose or change the medicine.

Yes, Clopidogrel is a blood thinner used to stop platelets from sticking together in turn reducing the risk of strokes or heart attack. CYP2C19 enzyme helps in conversion of Clopidogrel to its active metabolite.

The Clinical GENOMIST Implementation Consortium (CPIC) dosing guideline has recommended the following based on the GENOMISTreport.

As enough active drug will not be produced in individuals carrying CYP2C19 *2/*2 or *3/*3 or *2/*3 ( poor metabolizers), clopidogrel might not be able to stop platelets from sticking together leading to an increased risk for stroke. Therefore, if a person gets this report, an alternative antiplatelet therapy for CYP2C19 poor or intermediate metabolizers might be recommended.

We know that a change in the DNA is called a variant or polymorphism. In GENOMIST, we use the word “haplotype” to describe patterns of DNA variants that can be found in people.

A haplotype can have:

• A single variant
• Several variants that are found together

Depending on the changes which are in the haplotype, some haplotypes are associated with changes in protein function. Some genes use the “star alleles” system to name different haplotypes (e.g. *2, *17). Duplications of star alleles are shown by “xN (e.g. *1×2 i.e. duplication of *1 allele).

You can get following results based on your genotype:

• Major impact
  Risk of adverse drug reaction
  
  Your genetic profile indicates that your response to this drug might be hampered, increasing the risk for adverse reactions or might affect efficacy. A change in either dosage or alternative drug is suggested.
• Moderate impact
  Dosage change in medication maybe recommended
  
  

  Your genetic profile indicates that your response to this drug is not affected and no change in this drug is needed, if prescribed.

• Minimal impact
  No change in drug intake
  
  Your genetic profile indicates that your response to this drug is moderately/somewhat affected and a change in either dosage or an alternative drug may be indicated

• Continue the same medication
• Change the dose of a medication
• Stop taking a medication, or
• Prescribe a different medication

If a drug that you are currently using is indicated as ‘Major impact’ in the report, please refer to the indicated recommendation in the report and contact your doctor with this report to suggest any changes in your prescription. Do not change your medicine/drug intake without consulting your doctor.

If a drug that you are not using currently is indicated as ‘Major impact’ in the report, you do not need to add or change anything in your medication routine. Drugs/Medicines are prescribed by your doctor based on your current health conditions. In future, if these drugs are prescribed for you, please show this report to your doctor. This report will help your doctor make decisions on what drugs/medicines will work best for you and if they need to make changes in your medications.

PGx uses panel based testing by Next Generation Sequencing where data is filtered and analyzed to identify variants of interest and interpreted in the context of a single nucleotide polymorphisms associated with drug response.Haplotypes/ Diplotypes are reported according to the Human Genome Variation Society (HGVS).

GENOMIST alleles were manually curated from reviewed databases and published guidelines, CPIC, RNPgx, CPNDS and DPWG, and built into a database with relevant information. A list of data sources is provided under ‘References’. The report is generated through an automated pipeline that inputs genomic data generated through next generation sequencing or and GENOMIST alleles with high levels of evidence are matched with curated information for reporting.

• The current results are based on analysis of high levels of evidence variants as per published control studies of good quality relating to phenotype and/or genotype patients or healthy volunteers and having relevant pharmacokinetics or clinical endpoints. However, due to inherent technology limitations, deep intronic markers, certain structural and copy number variants are not covered.
• The result of this report cannot be extrapolated to a family member of the sampled individual.
• The classification and interpretation of all the variants in this assay reflects the current state of scientific understanding at the time this report was issued. Additional information may be available as new scientific information comes to light. Please contact laboratory in case re-analysis of the report is desired.

No, drug allergies are immune reactions to and transient for eg pennicillin rashes. This test is designed to report drug response based on genetic profile. These responses usually have more severe outcomes. Please note that some drug responses may show symptoms similar to drug allergy

Your treating physician should be able to help / guide on how you need to proceed with your treatment.

GenomeONE has multiple checks to ensure high-quality results. Our team of scientists and medical experts use a robust process to develop genetic reports for our customers.

Anyone can undergo pharmacogenomic testing to understand their drug response based on genetic profile. Your physician might recommend the test based on your health condition and drug response.

The results are valid for a lifetime as this is a DNA based test. Repeat testing would not be required. Your pharmacogenomics profile will be updated based on scientific advancements.