The clearest pharmacogenetic story medicine has had, and it is over. Two genotypes told you whether this regimen would work and whether it would make you anaemic — and then better drugs made the question stop mattering.
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
IFNL3 (historically IL28B) genotype is the strongest baseline predictor of response to peginterferon alfa and ribavirin in previously untreated hepatitis C, and CPIC published a guideline for using it as part of the shared decision to start that treatment. The context matters as much as the association: direct-acting antivirals have since replaced interferon-based regimens for most patients, and where they are used the predictive value of this genotype largely falls away. This is a pharmacogenetic marker that was close to standard of care and was overtaken by better drugs rather than by better genetics.
CPIC guidelines for IFNL3 (IL28B) genotype and PEG interferon-α-based regimens (Clin Pharmacol Ther 2014, PMID 24096968).
Ribavirin causes haemolytic anaemia in most patients who take it, severe enough to require a dose change in up to 15%. Variants causing inosine triphosphatase deficiency — a condition that had not been thought clinically important — protect against it. This is the unusual case of a genetic deficiency turning out to be an advantage in a specific pharmacological situation, and it predicts a side effect rather than whether the drug works.
Fellay et al., Nature 2010 — ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C (PMID 20173735).
Every guideline above was written by people. Named here because they are contributors to this page in the same sense anybody else on this site is.
These are the positions in your own file that carry the genes above. Not every gene in a guideline is one we report — where that is the case the gene appears above without a variant here, and the note says so.
ITPA · rs7270101
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