psoriatic arthritis genetics polymorphisms methotrexate therapy

Introduction

Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects both the skin and joints. Methotrexate (MTX) is a common treatment for PsA, but its efficacy and toxicity can vary significantly among patients. Genetic polymorphisms have been studied to understand their impact on the response to MTX therapy in PsA patients.

Key Insights

DHFR and MTHFR Polymorphisms:
- The minor A allele of the DHFR gene at +35289 is associated with a better response to MTX therapy in PsA patients.
- Patients homozygous for the MTHFR 677C/T (677TT) polymorphism have a higher risk of liver toxicity when treated with MTX.
Folate Pathway Polymorphisms:
- Polymorphisms in the folate pathway, such as RFC 80A and MTHFR 677C/T, are linked to both the efficacy and toxicity of MTX in psoriasis and PsA patients .
Efflux Transporter Genes:
- SNPs in efflux transporter genes like ABCC1 and ABCG2 are associated with a good response to MTX therapy and the onset of toxicity in psoriasis patients.
IL-6 Polymorphisms:
- The IL-6 -174 CC genotype is associated with an improved clinical outcome of MTX therapy in PsA patients, while the GC genotype is linked to a poorer response.
ANxA6 Gene Polymorphisms:
- The CC genotype of the ANxA6 gene (rs11960458) is significantly associated with a better response to MTX therapy in psoriasis patients.
Other Genetic Markers:
- Polymorphisms in genes such as GNMT, DNMT3b, and BHMT are associated with treatment outcomes and toxicity in psoriasis patients treated with MTX.
- Specific SNPs like rs216195T>C in SMG6, rs1050301G>A in IMMT, and rs2285421T>C in UPK1A have been identified as potential predictors of MTX efficacy in Chinese psoriasis patients.

Conclusion

Genetic polymorphisms play a significant role in determining the efficacy and toxicity of methotrexate therapy in psoriatic arthritis and psoriasis patients. Key genes involved include DHFR, MTHFR, RFC, IL-6, ANxA6, and various efflux transporters. Understanding these genetic markers can help in personalizing MTX therapy, potentially improving treatment outcomes and minimizing adverse effects.

Psoriatic arthritis genetics polymorphisms methotrexate therapy

Summary

Introduction

Key Insights

Conclusion

Sources and full results

Folate Pathway Enzyme Gene Polymorphisms and the Efficacy and Toxicity of Methotrexate in Psoriatic Arthritis

Polymorphisms of the DHFR gene may be associated with methotrexate efficacy and MTHFR 677TT may be related to liver toxicity in psoriatic arthritis patients.

Nucleotide Sequencing of Psoriatic Arthritis Tissue before and during Methotrexate Administration Reveals a Complex Inflammatory T Cell Infiltrate with Very Few Clones Exhibiting Features That Suggest They Drive the Inflammatory Process by Recognizing Autoantigens1

Psoriatic arthritis is driven by multiple inflammatory T cells, with few clones specifically recognizing autoantigens, and methotrexate treatment reduces inflammation but does not eliminate it.

Polymorphisms in folate, pyrimidine, and purine metabolism are associated with efficacy and toxicity of methotrexate in psoriasis.

Specific polymorphisms in folate, pyrimidine, and purine metabolism enzymes may help predict clinical response to methotrexate in psoriasis patients.

Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis.

Genetic variation in efflux transporter genes, particularly ABCC1, is associated with methotrexate efficacy and toxicity in patients with psoriasis.

Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms

Genetic variation in the methotrexate metabolic pathway may predict efficacy and toxicity in psoriasis treatment, potentially enhancing personalized medicine.

The impacts of gene polymorphisms on methotrexate in Chinese psoriatic patients

Gene polymorphisms may impact methotrexate efficacy in Chinese psoriatic patients, but their influence on treatment outcomes remains unclear.

Polymorphisms in GNMT and DNMT3b are associated with methotrexate treatment outcome in plaque psoriasis.

Polymorphisms in GNMT and DNMT3b genes are associated with poor methotrexate treatment outcomes in plaque psoriasis patients.

Relationship Between Interleukin-6 −174G/C Genetic Variant and Efficacy of Methotrexate Treatment in Psoriatic Arthritis Patients

The IL-6 174 G/C polymorphism may influence the efficacy of methotrexate treatment in psoriatic arthritis patients, but its association with psA susceptibility remains unclear.

The Impact of ANxA6 Gene Polymorphism on the Efficacy of Methotrexate Treatment in Psoriasis Patients

The CC genotype of ANxA6 (rs11960458) is significantly associated with a better response to methotrexate treatment in psoriasis patients, potentially predicting clinical efficacy of MTX therapy.

Genetic polymorphism predicting Methotrexate efficacy in Chinese patients with psoriasis vulgaris.

Three new SNPs identified in this study could predict methotrexate efficacy in Chinese patients with psoriasis vulgaris, potentially enabling precision medicine for this treatment.

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