Psoriatic arthritis genetics polymorphisms methotrexate therapy
Pro Research Analysisby 
Searched over 200M research papers
Consensus Meter
Genetic Polymorphisms and Methotrexate Therapy in Psoriatic Arthritis
Introduction to Psoriatic Arthritis and Methotrexate Therapy
Psoriatic arthritis (PsA) is a chronic inflammatory condition that affects both the skin and joints. Methotrexate (MTX) is a commonly used first-line treatment for PsA due to its efficacy in reducing symptoms and slowing disease progression. However, the response to MTX therapy varies significantly among patients, and genetic polymorphisms have been identified as potential factors influencing both the efficacy and toxicity of MTX.
Folate Pathway Gene Polymorphisms and MTX Efficacy
Research has shown that polymorphisms in genes involved in the folate pathway can impact the effectiveness of MTX therapy in PsA patients. Specifically, the minor A allele of the DHFR gene at +35289 has been associated with a better response to MTX therapy, with an odds ratio (OR) of 2.99, indicating a nearly threefold increase in the likelihood of a positive response. Conversely, the MTHFR 677TT genotype has been linked to increased liver toxicity, highlighting the importance of genetic screening in predicting adverse effects.
IL-6 Gene Polymorphisms and Clinical Outcomes
The IL-6 gene polymorphism, particularly the IL-6 -174 G/C variant, has been found to influence the clinical outcomes of MTX treatment in PsA patients. Those with the IL-6 -174 CC genotype showed a significantly better response to MTX therapy compared to those with GC or GG genotypes (P = 0.007). This suggests that IL-6 gene polymorphisms could serve as biomarkers for predicting MTX efficacy.
GNMT and DNMT3b Polymorphisms in Psoriasis
In patients with plaque psoriasis, polymorphisms in the GNMT and DNMT3b genes have been associated with MTX treatment outcomes. The GNMT rs10948059 variant was identified as a significant risk factor for treatment failure, with carriers having a sevenfold increased risk of inadequate response (OR, 6.94; p = 0.0004). Similarly, the DNMT3b rs2424913 variant was linked to a fourfold increased risk of treatment failure (OR, 4.10; p = 0.005). These findings underscore the potential of these genetic markers in guiding personalized MTX therapy.
ANxA6 Gene Polymorphisms and Long-term Efficacy
The ANxA6 gene polymorphisms, particularly rs11960458, have been associated with the long-term efficacy of MTX in psoriasis patients. Patients with the CC genotype of rs11960458 showed a higher likelihood of achieving significant clinical improvement (PASI75) compared to those with TT/CT genotypes (p = 0.019). This suggests that ANxA6 polymorphisms could be useful in predicting long-term treatment success.
Efflux Transporter Gene Polymorphisms and MTX Response
Polymorphisms in efflux transporter genes, such as ABCC1 and ABCG2, have also been linked to MTX response in psoriasis patients. The ABCC1 rs246240 variant was associated with both a good response to MTX and an increased risk of toxicity, with carriers of two copies of allele 1 having an OR of 2.2 for developing toxicity (P = 0.001). These findings highlight the role of efflux transporter genes in modulating MTX efficacy and safety.
Conclusion
Genetic polymorphisms play a crucial role in determining the efficacy and toxicity of methotrexate therapy in psoriatic arthritis and psoriasis patients. Polymorphisms in genes involved in the folate pathway, IL-6, GNMT, DNMT3b, ANxA6, and efflux transporters have all been identified as significant predictors of treatment outcomes. These insights pave the way for personalized medicine approaches, allowing for more tailored and effective MTX therapy based on individual genetic profiles. Further research and validation studies are needed to fully integrate these genetic markers into clinical practice.
Sources and full results
Most relevant research papers on this topic
Folate Pathway Enzyme Gene Polymorphisms and the Efficacy and Toxicity of Methotrexate in Psoriatic Arthritis
The impacts of gene polymorphisms on methotrexate in Chinese psoriatic patients
Methylenetetrahydrofolate reductase polymorphisms and methotrexate: no association with response to therapy nor with drug-related adverse events in an Italian population of rheumatic patients.
Relationship Between Interleukin-6 −174G/C Genetic Variant and Efficacy of Methotrexate Treatment in Psoriatic Arthritis Patients
Polymorphisms in GNMT and DNMT3b are associated with methotrexate treatment outcome in plaque psoriasis.
The Impact of ANxA6 Gene Polymorphism on the Efficacy of Methotrexate Treatment in Psoriasis Patients
Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms
Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis.
Genetic polymorphism predicting Methotrexate efficacy in Chinese patients with psoriasis vulgaris.
Genetic Polymorphisms of TYMS, MTHFR, ATIC, MTR, and MTRR Are Related to the Outcome of Methotrexate Therapy for Rheumatoid Arthritis in a Chinese Population
Try another search
What are the benefits and potential risks of high-protein diets for weight management and muscle building?
What are the latest treatments for anxiety disorders?
What are the different types of renewable energy sources and their efficiencies?
psychological flexibility procrastination anxiety
What are the basic building blocks of biomolecules?
What are the health impacts of long-term exposure to artificial lighting?