A Polymorphism (80G-&gt;A) in the Reduced Folate Carrier Gene and Its Associations with Folate Status and Homocysteinemia

Chango, Abalo; Emery-Fillon, Nathalie; Courcy, G. Potier De; Lambert, Daniel; Pfister, Michèle; Rosenblatt, David S.; Nicolas, Jean Francois Daniel

doi:10.1006/mgme.2000.3034

Cited by 283 publications

(238 citation statements)

References 21 publications

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“…However, the polymorphism could also directly impact disease activity through more subtle alteration in folate homeostasis. 15,18 In our study hepatotoxicity, measured as ALT and AST activities, after MTX treatment was observed in some 4-5% of patients and more frequently affected individuals with RFC-1 80AA (10.5%) genotype than 80GG genotype (2.3%). An increased toxicity observed in this group of patients may be related to elevated levels of MTX polyglutamates seen in RFC-1 80AA individuals.…”

Section: Discussionsupporting

confidence: 46%

“…The truncated protein alone is unable to transport MTX and is correctly considered non-functional. 13 The decreased affinity of RFC protein to MTX may be brought 15,17 In the present study, the influence of RFC-1 gene (G80A) polymorphism on treatment outcome with MTX of patients with RA was examined. The patients with RFC-1 AA genotype responded to the therapy more effectively than carriers of AG and GG genotypes.…”

Section: Discussionmentioning

confidence: 89%

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Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheumatoid arthritis

et al. 2007

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The folate antagonist methotrexate (MTX) is a drug currently used in the treatment of rheumatoid arthritis (RA). MTX enters the cells through the reduced folate carrier (RFC-1) and is activated to polyglutamates. Previous studies have shown that RFC-1 expression may influence the efficacy of therapy with MTX. The studies suggest that G80A polymorphism in RFC-1 is associated with altered folate/antifolate levels and the subjects carrying homozygous mutant 80AA genotype tend to have higher plasma folate and MTX concentrations and higher erythrocyte polyglutamate levels compared with those with the wild type or heterozygous genotype. It is possible that this polymorphism might influence MTX treatment outcome in patients with RA. In the present study, we examined the association between RFC-1 G80A polymorphism and treatment outcome in patients with RA administered MTX. The study was carried out on 174 patients diagnosed with RA treated with MTX (7.5-15.0 mg weekly) plus low doses of methylprednisone. The RFC-1 80G4A polymorphism (resulting in a histidine-to-arginine substitution at codon 27 of RFC-1) was detected using a polymerase chain reactionrestriction fragment length polymorphism method. The probability of remission of RA symptoms was 3.32-fold higher in carriers of 80AA genotype as compared with patients with 80GG genotype (P ¼ 0.021, OR ¼ 3.32,). The frequency of A allele among MTX responders was 62.1, compared to 47.8% in a group of poor MTX responders (P ¼ 0.013, OR ¼ 1.78, 95% CI: 1.13-2.81). Moreover, the increase of aminotransferase activity was noted more frequently in carriers of 80AA genotype. The present data suggest that evaluation of RFC-1 gene 80G4A polymorphism may be a useful tool to optimize MTX therapy in patients with RA.

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Section: Discussionsupporting

confidence: 46%

Section: Discussionmentioning

confidence: 89%

Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheumatoid arthritis

et al. 2007

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“…However, the combined heterozygosity for both C677T and A1298C mutations resulted in significant reduction of the MTHFR enzyme activity and plasma homocysteine elevations (van der Put et al, 1998). We do not know at this point about whether or not other recently discovered mutations such as G1793A mutation in the MTHFR gene (Rady et al, 2002), D919G mutation in methionine synthase gene (Chen et al, 2001), A66G mutation in methionine synthase reductase gene (Gaughan et al, 2001), G80A mutation in the RFC-1 folate transport protein gene might have played a role in the interaction of vitamin B status and homocysteine levels in our study subjects (Chango et al, 2000).…”

Section: Discussionmentioning

confidence: 81%

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

Kim

Chang

2003

Eur J Clin Nutr

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Objective: The purpose of this study was to investigate the effect of the interaction between the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes and serum levels of B vitamins on serum homocysteine levels in pregnant women. Design: A cross-sectional study. Setting: Ewha Womans University Hospital, Seoul, Korea. Subjects: A total of 177 normal pregnant women, 24.671.1 weeks of gestation, in a 6-month period during [2001][2002]. Interventions: Serum vitamin B 2 , vitamin B 6 , and homocysteine analyses were conducted using high-performance liquid chromatography methods. Serum folate and vitamin B 12 concentrations were determined using a radioimmunoassay kit. MTHFR gene mutation was investigated by the polymerase chain reaction of a genomic DNA fragment. Results: Serum homocysteine was higher in women with the T/T genotype than those with the C/T or C/C genotype of the MTHFR gene (Po0.05). Serum homocysteine was negatively correlated with serum folate in all MTHFR genotypes (Po0.001), and the correlation between the two serum levels was the strongest in the T/T genotype. Serum homocysteine was higher in the subjects with the T/T MTHFR genotype only when the serum folate was below the median level. Explanatory power of B vitamin status as predictors of serum homocysteine levels was more pronounced in the T/T genotypes (68.5%) compared with the C/T (37.9%) or C/C genotypes (20.6%). Conclusions: Serum homocysteine levels in pregnant women varied significantly with MTHFR genotype and the serum B vitamin status. Higher serum folate, vitamin B 2 , and vitamin B 12 concentrations may lessen the MTHFR genotypic effect on serum homocysteine levels.

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“…Considering the SLC19A1 gene encodes the RFC1 protein, it is plausible that polymorphism in SLC19A1 gene may interfere with the folate transporting by means of reduced SLC19A1 protein expression (De Table 2 continued Genotype and allele Marco et al 2003;Relton et al 2003). The effects of SLC19A1 G80A polymorphism on cellular folate intake remain uncertain (Whetstine et al 2001;StanislawskaSachadyn et al 2009); however, the G allele of G80A has been suggested as a risk factor for HHcy (Chango et al 2000;Altmae et al 2010), which is speculated to be associated with defective chorionic villous visualization in women with RPL (Nelen et al 2000). In the study, our findings were consistent with previous ones.…”

Section: Discussionmentioning

confidence: 99%

The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes

et al. 2014

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The aim of this study was to investigate the association between polymorphisms in folic acid metabolism-related genes and idiopathic recurrent early pregnancy loss (REPL). A prospective case-control study was performed on a cohort of 82 REPL patients and 166 healthy controls. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C was assessed by applying polymerase chain reaction for amplification followed by DNA sequencing, for methionine synthase reductase A66G, solute carrier family 19, member 1 (SLC19A1) G80A and C696T, and genotyping was done by utilizing the Sequenom MassARRAY system. The results revealed a significant association between MTHFR A1298C polymorphism and idiopathic REPL. Haplotype analysis indicated that the MTHFR 677C-MTHFR 1298C allele combination was associated with REPL (P \ 0.001). The MTHFR 677C-MTHFR 1298A and SLC19A1 80G-SLC19A1 696C allele combinations had lower frequencies in patients with REPL, but with P [ 0.05 (P = 0.093 and P = 0.084, respectively).

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A Polymorphism (80G->A) in the Reduced Folate Carrier Gene and Its Associations with Folate Status and Homocysteinemia

Cited by 283 publications

References 21 publications

Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheumatoid arthritis

Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheumatoid arthritis

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes

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