Association of MTHFR and RFC1 gene polymorphisms with methotrexate efficacy and toxicity in Chinese Han patients with rheumatoid arthritis

Abstract

Objective The objective was to explore the association of methylene tetrahydrofolate reductase ( MTHFR) C667T and A1298C and reduced folate carrier 1 ( RFC-1) A80G single nucleotide polymorphisms (SNP) with rheumatoid arthritis (RA) and efficacy and toxicity of methotrexate (MTX) treatment in Chinese Han patients in Henan, China. Methods Two hundred ninety-six patients with RA were enrolled (cases) and 120 healthy individuals served as controls. The genotypes of MTHFR C667T and A1298C SNP and RFC-1 A80G SNP were detected by restriction fragment length polymorphism-PCR and compared between cases and controls. We analyzed correlations of clinical effect, toxicity, and SNPs after 6 months of MTX treatment. Results We detected no significant differences in MTHFR C677T and A1298C and RFC-1 A80G SNPs between cases and controls. The RFC-1 A80G SNP differed between RA patients with good and poor efficacy after 6 months of MTX, and was an independent factor of MTX efficacy. The MTHFR C677T SNP was differently distributed in the adverse drug reaction (ADR) and non-ADR groups and was an independent factor of MTX toxicity. Conclusions In Chinese Han patients with RA, the MTHFR C667T SNP may correlate with MTX toxicity, whereas the RFC-1 A80G SNP may correlate with MTX efficacy rather than toxicity.

Genetic Polymorphisms of GGH and ABCC2 Are Associated with Methotrexate Intolerance in Patients with Rheumatoid Arthritis

“…According to several studies, the MTHFR variants A1298C and C677T are two of the most important polymorphisms associated with MTX toxicity [ 16 , 19 , 20 , 21 ]. The MTHFR A1298C polymorphism has been reported to lead to a 60% reduction in enzymatic activity in patients homozygous for 1298C, causing MTX intolerance [ 22 ].…”

Association Between MTHFR C677T Polymorphism and Susceptibility to Autism Spectrum Disorders: A Meta-Analysis in Chinese Han Population

“…The procedure of study selection is shown in Figure 1 , with the details of the inclusion and exclusion of studies illustrated. For pooling MAF, a total of 264 studies were identified from databases, among which 30 case-control studies were included for pooling minor allele prevalence ( 19 – 48 ), which all reported the MAF in non-ASD populations in Chinese Han. For the targeted gene effect, we yielded 119 papers initially and finally, six publications ( 49 – 54 ) were included in the present meta-analysis, with a total of 2,258 cases and 2,073 controls.…”

Influence of RFC1 c.80A>G Polymorphism on Methotrexate-Mediated Toxicity and Therapeutic Efficacy in Rheumatoid Arthritis: A Meta-analysis

“…Sensitivity analysis revealed that the exclusion of Wang et al 19 and Yamamoto et al 20 studies resulted in a borderline protective role of RFC1 A-allele against MTX toxicity 19,20 (Figure 4). Exclusion of other studies showed no difference in the association.…”

“…32 Robustness of meta-analysis was ensured by the sensitivity analysis. The exclusion of Wang et al 19 and Yamamoto et al 20 studies resulted in a borderline protective role of the RFC1 A-allele against MTX toxicity.…”