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KMID : 0882420040670020121
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Korean Journal of Medicine
2004 Volume.67 No. 2 p.121 ~ p.130
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Association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and methotrexate toxicity in korean patients with rheumatoid arthritis
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Kim Sung-Kyu
Jun Hey-Jung
Ahmed El-Sohemy
Park Yong-Wook
Lee Hye-Soon
Uhm Wan-Sik
Kim Tae-Hwan
Yoo Dae-Hyun
Bae Sang-Chul
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Abstract
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Background: This study was designed to identify the relationship between the C677T mutants of MTHFR and methotrexate toxicities in Korean patients with RA and to determine whether MTHFR polymorphism will be useful predictor for adverse effects of low dose methotrexate treatment.
Methods: We enrolled 385 (355 females, 30 males) patients with RA, who had been received low dose methotrexate. Genotypes of MTHFR polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The correlations between MTHFR genotypes, age, RF positivity, RA progression stage, KHAQ and adverse effects were analyzed by Spearman’s rank correlation test. The frequency analysis of C677T genotype and adverse effects was done by Chi-square test.
Results: The results of MTHFR genotypic analysis showed 133 patients (34.6%) with 677CC, 193 patients (50.1%) with 677CT and 59 patients (15.3%) with 677TT. One hundred fifty-four of the 385 patients (40.0%) had methotrexate-related side effects. The significant correlation between toxicities of methotrexate and MTHFR polymorphism was identified by Spearman’s rank correlation test (p<0.05). The odd ratio, which of adverse effects could be occurred by low dose methotrexate in rheumatoid arthritis patients with MTHFR polymorphism, showed higher value than other studies (p<0.001, OR: 4.0, 95% CI 2.45-6.51).
Conclusion: There was a positive association between methotrexate-related toxicities and MTHFR polymorphism. This study suggested that C677T mutant of MTHFR might be a powerful genetic indicator in predicting the adverse effects of low dose methotrexate therapy in patient with rheumatoid arthritis.(Korean J Med 67:121-130, 2004)
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KEYWORD
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Methylenetetrahydrofolate reductase, Rheumatoid arthritis, Methotrexate, Polymorphism, Adverse effects
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