The C677T polymorphism in the MTHFR gene is associated with the toxicity of methotrexate in a Spanish rheumatoid arthritis population

被引：51

作者：

Caliz, R. ^{[1
]}

del Amo, J. ^{[2
]}

Balsa, A. ^{[3
]}

Blanco, F. ^{[4
]}

Silva, L. ^{[5
]}

Sanmarti, R. ^{[6
]}

Martinez, F. G. ^{[7
]}

Collado, M. D. ^{[1
]}

del Carmen Ramirez, M. ^{[1
]}

Tejedor, D. ^{[2
]}

Artieda, M. ^{[2
]}

Pascual-Salcedo, D. ^{[3
]}

Oreiro, N. ^{[4
]}

Andreu, J. L. ^{[5
]}

Graell, E. ^{[6
]}

Simon, L. ^{[2
]}

Martinez, A. ^{[2
]}

Mulero, J.

机构：

[1] Virgen Nieves Univ Hosp, Granada, Spain

[2] Progenika Biopharma SA, Derio, Vizcaya, Spain

[3] La Paz Univ Hosp, Madrid, Spain

[4] Hosp Juan Canalejo, Coruna, Spain

[5] Puerta de Hierro Univ Hosp, Madrid, Spain

[6] Hosp Clin Barcelona, Barcelona, Spain

[7] Univ Hosp, Cordoba, Spain

来源：

SCANDINAVIAN JOURNAL OF RHEUMATOLOGY | 2012年 / 41卷 / 01期

关键词：

LOW-DOSE METHOTREXATE; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; SINGLE-NUCLEOTIDE POLYMORPHISMS; EFFICACY; FOLATE; THERAPY; DISEASE; ENZYMES; METAANALYSIS; DRUGS;

D O I：

10.3109/03009742.2011.617312

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: Methotrexate (MTX) is the first-choice drug for the treatment of rheumatoid arthritis (RA) patients. However, 30% of RA patients discontinue therapy within 1 year, usually because of adverse effects. Previous studies have reported conflicting results on the association of polymorphisms in the MTHFR gene with the toxicity of MTX in RA. The aim of this study was to assess the involvement of the C677T and A1298C polymorphisms in the MTHFR gene in the toxicity of MTX in a Spanish RA population. Methods: The study included retrospectively 468 Spanish RA patients treated with MTX. Single nucleotide polymorphism (SNP) genotyping was performed using the oligonucleotide microarray technique. Allele and genotype association analyses with regard to MTX toxicity and a haplotype association test were also performed. Results: Eighty-four out of the 468 patients (18%) had to discontinue therapy due to adverse effects or MTX toxicity. The C677T polymorphism (rs1801133) was associated with increased MTX toxicity [odds ratio (OR) 1.42, 95% confidence interval (CI) 1.01-1.98, p = 0.0428], and the strongest association was shown in the recessive model (OR 1.95, 95% CI 1.08-3.53, p = 0.0246). The A1298C polymorphism (rs1801131) was not associated with increased MTX toxicity (OR 0.94, 95% CI 0.65-1.38, p = 0.761). A borderline significant risk haplotype was found: 677T-1298A (OR 1.40, 95% CI 1.00-1.96, p = 0.0518). Conclusion: These results demonstrate that the C677T polymorphism in the MTHFR gene is associated with MTX toxicity in a Spanish RA population.

引用

页码：10 / 14

页数：5

共 34 条

[21] Evidence from clinical trials and long-term observational studies that disease-modifying anti-rheumatic drugs slow radiographic progression in rheumatoid arthritis: updating a 1983 review [J].