Genetic Determinants of Methotrexate Toxicity in Tunisian Patients with Rheumatoid Arthritis: A Study of Polymorphisms Involved in the MTX Metabolic Pathway

Abstract

The results demonstrated that the C677T polymorphism in the MTHFR gene is associated with MTX toxicity in Tunisian RA patients. In contrast, the TYMS 2R/3R polymorphism is associated with a protective effect against overall MTX toxicity.

Lack of association between MTHFR A1298C polymorphism and outcome of methotrexate treatment in rheumatoid arthritis patients: evidence from a systematic review and meta‐analysis

“…The initial search identified 116 articles. Among these, a total of 22 studies encompassing 3346 RA patients, were found to be eligible for further analysis according to our inclusion criteria (Fig. ).…”

“…The association between MTHFR A1298C SNP and MTX treatment efficacy in RA was reported in four studies, while 12 studies reported an association with toxicity and six studies provided data for both efficacy and toxicity. Overall, the data from 10 studies (1325 RA patients) was analyzed for determining the correlation between A1298C polymorphism and efficacy, and 18 studies (2777 RA patients) were included for the toxicity analysis.…”

“…Regarding the details of the studies, eight studies had small sample sizes (fewer than 100 cases) whereas 14 studies had large sample sizes (more than 100 cases) . In addition, the studies included patients of different ethnicities, with 11 studying Caucasian populations, five East Asian populations, two South Asian populations, one a Jewish population, one a Latin American population and two mixed‐ethnicity populations. Nineteen studies provided the full distribution of AA, CA and CC genotypes, and three studies provided the frequencies of AA and CA + CC genotypes.…”

“…In addition, the studies included patients of different ethnicities, with 11 studying Caucasian populations, five East Asian populations, two South Asian populations, one a Jewish population, one a Latin American population and two mixed‐ethnicity populations. Nineteen studies provided the full distribution of AA, CA and CC genotypes, and three studies provided the frequencies of AA and CA + CC genotypes. Based on the criteria used for toxicity evaluation, 14 studies analyzed adverse effects of MTX, whereas three studies analyzed toxicity related to MTX discontinuation.…”

“…Regarding efficacy, three different meta‐analyses observed similar results with relatively small numbers of subjects (692, 743 and 1040, respectively). In the past 3 years, seven additional studies have been conducted to detect the association between MTHFR A1298C polymorphism and MTX response, and thus, it is necessary to perform a larger updated meta‐analysis to confirm this association based on all the studies out there in the literature.…”