Can our DNA tell neurologists upfront whether interferon‑β will actually work?

Relapsing–remitting multiple sclerosis (RRMS) often begins with interferon‑β (IFN‑β) injections, yet nearly half of patients discover—after months or even years—that the drug never really slowed their relapses or disability. That costly “wait‑and‑see” approach drains both time and hope. A 2017 genome‑wide association study (GWAS) asked whether common DNA variants could sort responders from non‑responders before the first syringe is opened.

How the study was built
The investigators ran a two‑stage GWAS. First, they scanned 151 Australians whose genomes had already been typed for MS‑risk studies—51 clear responders, 76 clear non‑responders and 24 intermediates. Next, they tried to replicate every promising signal in 479 fresh patients from Australia, Spain and Italy (273 responders, 206 non‑responders). An “extreme‑phenotype” design amplified the contrast, while the MAX4 efficiency‑robust test compared four inheritance models in one sweep to ensure no real association slipped past.

What they found
No single variant smashed the classic genome‑wide significance bar, but eight single‑nucleotide polymorphisms (SNPs) consistently nudged treatment outcome in the same direction across both cohorts. Two sat in protein‑coding genes—FHIT on chromosome 3 and GAPVD1 on chromosome 9—while the rest mapped to zinc‑finger territory or uncharted intergenic stretches. Importantly, several acted as expression quantitative‑trait loci (eQTLs), hinting they tweak gene activity rather than protein sequence.

Why these genes might matter
FHIT encodes a fragile‑site tumour suppressor that also reins in the NF‑κB pathway, a master switch of pro‑inflammatory cascades that IFN‑β is meant to calm.

GAPVD1 orchestrates endocytosis and insulin‑receptor trafficking; glitches here could alter how immune cells recycle their interferon receptors or route downstream signals.

The zinc‑finger locus near ZNF697 plus three intergenic hits may hide enhancers or silencers that fine‑tune immune activation, though their exact choreography awaits bench‑top dissection.

Clinically, what changes tomorrow?
If future studies validate these loci, neurologists could one day run a rapid DNA panel during treatment planning. Patients with an “unfavourable” genotype might skip IFN‑β altogether and move straight to another disease‑modifying therapy, sparing them 18‑plus months of ineffective injections and possible side‑effects. The study also confirmed that these eight SNPs do not predict response to glatiramer acetate, underscoring their drug‑specific signal rather than a generic “mild‑disease” tag.

Caveats and next steps
Sample sizes were modest by GWAS standards, keeping p‑values just shy of the million‑test threshold. Neutralising‑antibody data—one known reason for IFN‑β failure—were unavailable, and rare variants invisible to genotyping chips could still carry larger effects. The authors call for international registries such as MSBase and next‑generation sequencing to close those gaps.

Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.

References:
Mahurkar, S., Moldovan, M., Suppiah, V. et al. Response to interferon-beta treatment in multiple sclerosis patients: a genome-wide association study. Pharmacogenomics J 17, 312–318 (2017). https://doi.org/10.1038/tpj.2016.20