How can genetic variation in HLA antigens influence drug therapy outcomes?

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BlackTom AI · Accepted Answer

The question asks how genetic variation in HLA antigens can influence drug therapy outcomes. 
Option 1: 'By predicting the risk of hypersensitivity reactions' aligns with established pharmacogenomics knowledge. Certain HLA alleles are strongly associated with hypersensitivity reactions to specific drugs (for example, HLA-B*1502 and Stevens-Johnson syndrome with some anticonvulsants, or HLA-B*57:01 with abacavir). This variation helps identify individuals at higher risk, guiding safer prescribing or closer monitoring. 
Option 2: 'By altering the rate of drug absorption' is not a typical consequence of HLA antigen variation. Absorption is primarily influenced by properties of the drug and GI physiology, not HLA gene variants, which are related to immune recognition rather than pharmacokinetic absorption processes. 
Option 3: 'By changing the drug’s mechanism of action' is inaccurate. HLA antigens are immune system components; they do not inherently change how a drug exerts its pharmacodynamic effect on its molecular target. They influence immune-mediated adverse effects more than the drug’s primary mechanism. 
Option 4: 'By modifying the drug’s solubility' is not a plausible link. Solubility is dictated by physicochemical properties and formulations, not by genetic variation in HLA antigens, which would not alter a drug’s solubility in body fluids. 
Putting the pieces together, the clinically meaningful impact of HLA variation is most consistently described as the ability to predict risk of immune-mediated adverse reactions, particularly hypersensitivity, thereby informing safer use of certain medications.

PCOL2021 2025 Practice MCQ Section A - 2025

How can genetic variation in HLA antigens influence drug therapy outcomes?

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