General pharmacology and pharmacokinetics: warfarin pharmacogenetics: practice question

A Pharmacology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pharmacology · General pharmacology and pharmacokinetics: warfarin pharmacogenetics

Sample item

An elderly patient needs only 1.5 mg of warfarin daily to hold the INR at 2.5, far below the usual requirement. Genotyping shows a variant in the gene that encodes warfarin's own target enzyme. Which gene is it?

ATPMTBNAT2CCYP2D6DVKORC1

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

D. VKORC1

Warfarin inhibits vitamin K epoxide reductase, encoded by VKORC1. Variants that lower enzyme expression make patients unusually sensitive, so low doses suffice. CYP2C9 variants also reduce dose requirements, but that gene encodes the metabolising enzyme and not the target.

Option by option

A. TPMT
TPMT metabolises thiopurines such as azathioprine and 6-mercaptopurine.
B. NAT2
NAT2 acetylates drugs such as isoniazid and hydralazine.
C. CYP2D6
CYP2D6 metabolises drugs such as codeine and tamoxifen, and is not warfarin's target.
D. VKORC1 (correct)
Correct. VKORC1 encodes the vitamin K epoxide reductase complex that warfarin inhibits.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is D, VKORC1. Warfarin inhibits vitamin K epoxide reductase, encoded by VKORC1.

Why is "TPMT" not the answer?

TPMT metabolises thiopurines such as azathioprine and 6-mercaptopurine.

Why is "NAT2" not the answer?

NAT2 acetylates drugs such as isoniazid and hydralazine.

Why is "CYP2D6" not the answer?

CYP2D6 metabolises drugs such as codeine and tamoxifen, and is not warfarin's target.

What concept does this question test?

It tests General pharmacology and pharmacokinetics: warfarin pharmacogenetics in Pharmacology. Variants that lower enzyme expression make patients unusually sensitive, so low doses suffice. CYP2C9 variants also reduce dose requirements, but that gene encodes the metabolising enzyme and not the target.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study General pharmacology and pharmacokinetics: warfarin pharmacogenetics?

Learn drugs as classes, then the exception in each class that an examiner would pick. Then use the flashcards and the other Pharmacology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.