Unlocking Truly Personalised Treatments
The secret to defeating psoriasis might be written in our genes.
For millions living with psoriasis, finding an effective treatment can be a long and frustrating journey. What if a simple genetic test could predict which treatment would work best for you? This is the promise of pharmacogenetics—the study of how our genes affect our response to drugs. Researchers are now decoding the genetic variations that make every case of psoriasis unique, bringing us to the brink of a new era where treatments are tailored to an individual's DNA, maximizing effectiveness and minimizing side effects.
At its core, psoriasis is a complex dance between genetic predisposition and environmental triggers. While not caused by a single gene, an individual's risk of developing psoriasis and their likely response to treatment is heavily influenced by genetic polymorphisms—small, natural variations in our DNA sequence that make each of us unique 1 .
The most common type of these variations are called Single Nucleotide Polymorphisms (SNPs), where a single building block of DNA is altered in a specific location of the genome 1 . Think of it as a single typo in a massive instruction manual.
This allele is associated with earlier onset and more severe psoriasis 1 .
Identify psoriatic arthritis early
Predict cardiovascular complications
Forecast treatment response
To understand how this groundbreaking research works in practice, let's examine a real-world study, dubbed the BROADEN study, which investigated the genetic factors behind response to the biologic drug brodalumab 5 .
119 patients with plaque psoriasis from 11 Spanish hospitals 5 .
Optimal response = PASI score ≤1 after 6 and 12 months 5 .
Screened for 180 different polymorphisms using custom microarray 5 .
Statistical analysis to find genetic variations in super-responders 5 .
The study yielded compelling results. While 68% of patients achieved super-responder status at 6 months, the genetic associations became most pronounced after a full year of treatment 5 .
| Gene/SNP ID | Genotype | Effect on Treatment Response |
|---|---|---|
| SPATA2 (rs495337) | AG or AA | Increased probability of optimal response (PASI ≤1) |
| HTR2A (rs6311) | CT or TT | Risk factor for not achieving optimal response |
| LCE3D (rs4085613) | GT | Risk factor for not achieving optimal response |
These findings suggest that a genetic test could help dermatologists determine if brodalumab is the best initial choice for a particular patient, potentially saving time, cost, and frustration 5 .
| Biological Drug | Target | Associated Gene/SNP | Impact on Response |
|---|---|---|---|
| Tildrakizumab | IL-23 | TNFAIP3 (rs610604) | GG genotype = risk factor for suboptimal response 7 |
| Anti-IL-12/23 | IL-12/23 | PGLYRP4 (rs2916205) | Associated with long-term efficacy 9 |
| Anti-TNF Therapy | TNF-alpha | TNFAIP3, IL17RA | Various SNPs influence response 1 4 |
| Ustekinumab | IL-12/23 | HLA-Cw*06 | Better and quicker response in carriers 1 |
The quest to personalize psoriasis treatment relies on a sophisticated array of laboratory technologies. Here are some of the key tools enabling these discoveries.
Sequences all protein-coding regions of a genome. A cost-effective method to find DNA changes that predispose individuals to psoriasis 1 .
Rapidly sequences entire genomes or targeted regions. Provides a deep, comprehensive view of genetic makeup 1 .
The field of psoriasis pharmacogenetics is rapidly advancing beyond predicting drug response. The future points toward true disease modification—treatments that can alter the underlying course of the disease, potentially leading to long-term remission even after therapy is stopped 2 3 .
Research shows that early intervention with biologics, especially in patients with a shorter disease history, can significantly increase the chances of sustained remission 2 .
Future treatments may combine biologics with drugs designed to erase "epigenetic scarring"—long-lasting changes to skin cells that prime them for inflammation 2 .
From CRISPR-based gene editing to therapies that "re-educate" misguided immune cells, the future holds promise for truly transformative treatments 2 .
As research continues to unravel the complex genetic tapestry of psoriasis, the day when a dermatologist can confidently say, "This is the right treatment for you, based on your DNA," is drawing nearer.