Related Experiment Video
Updated: Sep 25, 2025
Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
MTHFR Gene Polymorphism Association With Psoriatic Arthritis Risk and the Efficacy and Hepatotoxicity of Methotrexate
Jie Zhu1, Zhicheng Wang2, Lu Tao1
1Shanghai Institute of Dermatology, Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
Aims:
To assess whether MTHFR rs1801131 and rs1801133 SNPs are associated with concomitant psoriatic arthritis (PsA) and investigate the efficacy and hepatotoxicity of MTX in patients with psoriasis in the Han Chinese population.
Methods:
This prospective, single-arm, interventional study recruited a total of 309 patients with psoriasis, 163 with psoriatic arthritis and 146 without psoriatic arthritis, who completed a 12-week MTX treatment and 1,031 healthy controls. Patients' characteristics including age, gender, disease duration, height, weight, smoking status, alcohol consumption, medical history, disease severity and liver function test results were accessed and recorded. Single nucleotide polymorphism (SNP) genotyping of rs1801131 and rs1801133 in the MTHFR gene was performed.
Results:
The rs1801133 CC genotype was more frequent in patients with PsA than those with PsO and healthy controls (42.3% vs. 28.8% vs. 33.1%, p < 0.05). The 90% reduction from baseline PASI score (PASI 90) response rates to MTX were significantly higher in patients with the rs1801133 TT genotype than those with the CT and CC genotype (33.96% vs. 19.31% vs. 14.41%, OR = 2.76, p = 0.006). The rs1801133 CT+TT genotype was more frequent in PsA patients with abnormal liver function than in those with normal liver function (p < 0.05). In addition, patients with the rs1801131 CT genotype had lower PASI 75 response rates to MTX (OR = 0.49, p = 0.01), and lower risk of ALT elevation (OR = 0.46, p = 0.04).
Conclusions:
This study provided some evidence for MTHFR polymorphism association with the risk of PsA and the efficacy and hepatotoxicity of the low-dose MTX in the Chinese population. Given the relatively small sample size and potentially missed diagnosis of PsA, the results from this study warrant further investigation.
Insights
MTHFR gene variants are linked to psoriatic arthritis (PsA) risk and methotrexate (MTX) treatment outcomes in Chinese patients. Specific MTHFR genotypes influence MTX efficacy and hepatotoxicity, suggesting personalized treatment approaches.
Area of Science:
- Genetics and Rheumatology
- Pharmacogenomics
- Clinical Medicine
Background:
- Psoriatic arthritis (PsA) is a chronic inflammatory condition often treated with methotrexate (MTX).
- The methylenetetrahydrofolate reductase (MTHFR) gene plays a role in folate metabolism, potentially influencing drug response and disease risk.
- Genetic variations in MTHFR may impact MTX efficacy and toxicity in patients with psoriasis and PsA.
Purpose of the Study:
- To investigate the association between MTHFR gene polymorphisms (rs1801131 and rs1801133) and the risk of developing PsA in Han Chinese patients with psoriasis.
- To evaluate the impact of these MTHFR SNPs on the efficacy (PASI 90 and PASI 75 response) and hepatotoxicity (ALT elevation) of low-dose MTX treatment.
Main Methods:
- A prospective study involving 309 patients with psoriasis (163 with PsA, 146 without) and 1031 healthy controls.
- Genotyping of MTHFR rs1801131 and rs1801133 single nucleotide polymorphisms (SNPs).
- Assessment of 12-week MTX treatment response and liver function tests, correlating outcomes with MTHFR genotypes.
Main Results:
- The rs1801133 CC genotype was more prevalent in PsA patients compared to psoriasis patients and healthy controls (p < 0.05).
- Patients with the rs1801133 TT genotype showed significantly higher PASI 90 response rates to MTX (OR = 2.76, p = 0.006).
- The rs1801133 CT+TT genotype was associated with increased risk of abnormal liver function (p < 0.05), while rs1801131 CT genotype was linked to lower PASI 75 response and reduced risk of ALT elevation.
Conclusions:
- MTHFR gene polymorphisms are associated with PsA risk and MTX treatment outcomes in the Han Chinese population.
- Specific MTHFR genotypes may predict MTX efficacy and hepatotoxicity, offering potential for personalized medicine.
- Further research with larger sample sizes is recommended due to the study's limitations.
Related Concept Videos
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
01:20Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
01:17Phase II Reactions: Methylation Reactions
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...