miRNA-24 Gene Sequence, DHFR -829C-T Genotypes, and Methotrexate Response in Mexican Patients with Rheumatoid Arthritis

墨西哥类风湿性关节炎患者的 miRNA-24 基因序列、DHFR -829C-T 基因型和甲氨蝶呤反应

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作者:Martha Rocio Hernández-Preciado, María Cristina Morán-Moguel, Ingrid Patricia Dávalos-Rodríguez, Christian Michel Enríquez-Barajas, Juan Paulo Valdovinos-Maravilla, Ana Lilia Díaz-Pérez, Daniel Efraín Silva-Castro, Laura González-López, Jorge Ivan Gámez-Nava, Mario Alberto Aceves-Aceves, Mario Salaz

Aim

The present study looked for variation in the miRNA-24 sequence, and evaluated the associations between the dihydrofolate reductase (DHFR) gene-829 C-T polymorphism and plasma DHFR concentrations with response to methotrexate (MTX) treatment in Mexican patients with rheumatoid arthritis (RA).

Conclusion

The -829C-T polymorphism of DHFR gene was not associated with response to MTX by RA patients, and no variations were found in the miRNA-24 sequence that might modify the response to treatment or DHFR enzyme levels in a Mexican population with RA.

Methods

A total of 135 women with RA were classified as responders (disease activity score [DAS28] <3.2) or nonresponders to MTX (DAS28 > 3.2). We determined the genotype of the patients using the polymerase chain reaction-restriction fragment length polymorphism method. Plasma DHFR enzyme levels and mi-RNA24 sequences were assessed by enzyme-linked immunosorbent assay (ELISA) and Sanger sequencing, respectively. Allelic frequencies and the genotypic distribution of the polymorphism were analyzed by the chi-square test.

Results

The genotype frequencies of the DHFR -829C-T polymorphism among responders were 37.0% CC, 52.1% CT, and 10.9% TT and for nonresponders were 33.9% CC, 56.4% CT, and 9.7% TT. No significant differences in genotype frequencies were found between the groups (p = 0.88). The DHFR levels relative to genotype for responders were 6.8 ± 2.7, 6.1 ± 2.7, and 6.5 ± 1.5 ng/mL for CC, CT, and TT, respectively, and for nonresponders were 6.5 ± 2.0, 6.1 ± 3.1, and 7.4 ± 1.8 ng/mL for CC, CT, and TT, respectively. No significant differences were found between the two groups. Similarly, both groups showed no sequence variations in miRNA-24 gene.

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