Maarg Manthan · Topic 10.17

Pharmacogenetics

Science & Technology › Biotechnology – Principles and Techniques · Topic 10.17

Pharmacogenetics is the study of how differences in a persons genes change the way the body responds to a drug, including how fast it is broken down, how well it works and whether it causes side effects. Pharmacogenomics is the wider form that looks at the whole genome. Variants in genes for drug metabolising enzymes, such as the cytochrome P450 family, drug transporters and drug targets decide whether a person is a poor, normal, rapid or ultrarapid metaboliser. The aim is to give the right drug at the right dose to the right person, which reduces adverse reactions and wasted treatment, and forms a key part of precision medicine.

5 min read · UPSC Prelims · Science & Technology · Biotechnology – Principles and Techniques

At a Glance

Study of Gene effect on drug response
Key enzymes Cytochrome P450 family
Outcome Right drug, right dose
Wider field Pharmacogenomics
Link Precision medicine
Exam link UPSC Prelims, Science & Technology: Biotechnology – Principles and Techniques

Where Does It Fit?

This topic follows systems biology. Pharmacogenetics is one of the most practical results of the idea that each person differs, and it puts genomic data to use in prescribing. Previous topic: Systems Biology and Its Application to Medicine. Next topic: Diagnostics in Developing Countries.

How Do Genes Change Drug Response?

Gene or enzyme	Effect on drugs
CYP2D6	Breaks down many drugs including codeine. Ultrarapid metabolisers may turn codeine into too much morphine, while poor metabolisers get little pain relief
CYP2C19	Activates the antiplatelet drug clopidogrel. Poor metabolisers get less benefit and have a higher risk of clots
CYP2C9 and VKORC1	Affect the dose of the blood thinner warfarin
TPMT	Affects breakdown of thiopurine drugs used in leukaemia and autoimmune disease. Low activity can cause severe bone marrow damage
HLA-B5701 and HLA-B1502	Immune gene variants linked to serious reactions to abacavir and carbamazepine
G6PD deficiency	Some drugs, such as primaquine and rasburicase, cause red cell destruction in people with this inherited enzyme deficiency
NAT2	Controls acetylation of isoniazid, a tuberculosis drug, so slow acetylators are at risk of toxicity

What Are the Uses and Limits?

Dose selection: genetic tests guide warfarin and thiopurine doses
Drug choice: testing before starting abacavir or carbamazepine avoids severe allergic reactions
Cancer therapy: tumour gene changes guide targeted drugs, such as HER2 for trastuzumab and EGFR for gefitinib
Avoiding adverse reactions: adverse drug reactions are a major cause of hospital admission
Drug development: trials can select patients likely to respond
Population differences: variant frequencies differ between ethnic groups, so Indian data are needed
Cost and access: tests are not yet widely available in public health systems
Data and consent: genetic data need privacy protection

What Else Should You Remember?

Polymorphism: a gene variant present in at least one per cent of the population, which often explains drug response
Metaboliser types: people are classed as poor, intermediate, extensive or ultrarapid metabolisers
Prodrugs: some drugs, such as clopidogrel and codeine, are inactive until the body converts them, so a poor converter gets less effect
Single nucleotide polymorphism: a change in one DNA base is the most common type of variant
Guidelines: the Clinical Pharmacogenetics Implementation Consortium and regulators publish gene and drug pairs and dosing advice
India: the Council of Scientific and Industrial Research and other bodies have studied Indian gene variants through projects such as the Indian Genome Variation Consortium
Pharmacovigilance: the Pharmacovigilance Programme of India collects reports of adverse drug reactions
GenomeIndia: reference data from Indian populations will improve drug response research, as in Genomics and Proteomics
Pharmacogenetics versus pharmacogenomics: the first studies single gene effects, while the second looks at many genes across the genome
Limits: drug response also depends on age, diet, other drugs and disease, so genes are only one factor
Doctors training: prescribers need training to interpret results
Link: precision medicine uses these results, as in Systems Biology and Its Application to Medicine
Warfarin example: the dose that is safe for one patient can cause bleeding in another, and tests for CYP2C9 and VKORC1 variants help to set the starting dose
Cost effectiveness: testing is worth the cost mainly where severe reactions are common and a safe alternative exists
Newborn and cancer uses: tests before starting some cancer drugs prevent severe toxicity and improve survival
Ethnic variation: the frequency of many drug response variants differs between Indian groups and other populations, so guidelines made elsewhere cannot always be copied

Why Does It Matter for the Exam?

Definition: pharmacogenetics versus pharmacogenomics
Examples: CYP enzymes, warfarin and G6PD
Application: precision medicine
Current affairs link: Indian genome projects and drug safety
Common errors: saying that pharmacogenetics changes a persons genes

As an analytical point, pharmacogenetic testing can make prescribing safer and cheaper in the long run. India needs its own variant data and clear guidelines so that testing is used where it adds clear benefit.

Why Is This Topic Important?

Concept Gene and drug
Examples Enzymes asked
Policy Precision medicine

What Came Next?

The next topic covers diagnostics in developing countries. Next topic: Diagnostics in Developing Countries.

Key People and Terms

Polymorphism Common gene variant
CYP450 Drug metabolising enzymes
Prodrug Drug activated in body
Metaboliser Speed of drug breakdown
Adverse reaction Harmful drug effect
Allele Version of a gene

Exam Corner

Points to Remember

CYP enzymes are in the liver.
Clopidogrel needs CYP2C19.
G6PD deficiency: avoid primaquine.
Pharmacogenetics does not change genes.
Goal: right drug, right dose.

Do Not Confuse With

Pharmacogenetics and gene therapy Predicting drug response versus changing genes
Pharmacogenetics and pharmacogenomics One gene versus whole genome
Pharmacokinetics and pharmacodynamics What the body does to the drug versus what the drug does to the body

Memory Hook

Genes decide the pace, the dose must fit the case; the right drug for the right face.

Mains Angle

Questions ask about the concept and examples. These points help.

Concept Gene effect on drug
Benefit Safety and efficacy
Issues Cost and data

A Question You May Face

An original practice question, not a past paper question.

“What is pharmacogenetics? Discuss its importance and the challenges in applying it in public health in India.”

How to Answer

Concept Gene and drug response.
Examples CYP, G6PD.
Benefits Safer prescribing.
Way Indian data, training.

GS Relevance

Prelims: meaning, enzymes, examples, precision medicine. GS Paper 3: science and technology, biotechnology, health.

Frequently Asked Questions

What is pharmacogenetics?

Pharmacogenetics is the study of how a persons genes affect their response to drugs, including the speed of drug breakdown, the effectiveness of treatment and the risk of side effects. It helps doctors to choose the right drug and dose for each patient, and is a key part of precision medicine.

What is the difference between pharmacogenetics and pharmacogenomics?

Pharmacogenetics usually studies the effect of one or a few genes on drug response, while pharmacogenomics studies the combined effect of many genes across the whole genome. In practice the two terms are often used together, and both aim to personalise drug treatment on the basis of genetic information.

Why does G6PD deficiency matter for drug use?

G6PD deficiency is an inherited lack of an enzyme that protects red blood cells. In affected people, certain drugs such as primaquine, used for malaria, can destroy red cells and cause haemolytic anaemia. Testing before using such drugs prevents serious harm, particularly in India where the deficiency is common in some groups.

What are cytochrome P450 enzymes?

Cytochrome P450 enzymes are a family of liver enzymes that break down or activate many drugs. Gene variants in enzymes such as CYP2D6 and CYP2C19 make some people poor or ultrarapid metabolisers, changing the effect of drugs such as codeine and clopidogrel and sometimes needing a different dose or drug.

How can pharmacogenetics reduce side effects?

Pharmacogenetic tests identify patients who carry gene variants linked to severe reactions, for example HLA-B*5701 with abacavir, so doctors can choose a safer drug before treatment begins. Testing also guides doses of drugs such as warfarin, which lowers the risk of bleeding and treatment failure.

PYQ Practice — Statement Analysis

1 Pharmacogenetics studies how genes influence the response to drugs.

True

The central idea.

2 G6PD deficiency can cause red cell destruction after exposure to certain drugs.

True

For example primaquine.

3 Pharmacogenetic testing changes the DNA of the patient.

False

It only reads genes.

4 CYP450 enzymes are mainly found in the kidney.