Plasma total homocysteine level and methylenetetrahydrofolate reductase 677C>T genetic polymorphism in Japanese patients with rheumatoid arthritis

Abstract

Hyperhomocysteinemia is a known risk factor of cardiovascular disease. Homocysteine has been also linked to inflammation in rheumatoid arthritis (RA). In this study, we investigated the relationship between plasma homocysteine levels and single nucleotide polymorphism (SNP) of the gene coding for methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the biosynthesis of homocysteine, and the correlation between the plasma homocysteine levels and generally used inflammatory markers (C-reactive protein, erythrocyte sedimentation rate and matrix metalloproteinase-3) in 96 Japanese patients with RA. Plasma homocysteine levels in patients with the MTHFR 677TT genotype were significantly higher than in those with the 677CC genotype (p < 0.05). In addition, plasma homocysteine levels were increased along with the elevation of general inflammatory markers. Therefore, we conclude that homocysteine might affect the inflammatory status of patients, and the MTHFR 677C>T SNP could be a predictive factor of hyperhomocysteinemia in patients with RA.

Role of Genetic and Acquired Prothrombotic Risk Factors in Genesis of Sudden Sensorineural Hearing Loss

“…In the literature, the association between MTHFR C677T mutation and hyperhomocysteinemia has been confirmed by various authors [Almawi et al, 2009;Fujimaki et al, 2009;Husemoen et al, 2009;Oterino et al, 2010;Szamosi et al, 2009;Yamada et al, 2001] although in another study [Antoniades et al, 2009] the same mutation showed a stronger correlation with low folate levels. In our study we did not analyze folate levels; however, according to several studies, low levels of folate are inversely related to homocysteine levels [Cadoni et al, 2004;Quaranta et al, 2008;Schuknecht et al, 1973;Suckfüll et al, 2002].…”

Antiphospholipid antibodies and atherosclerosis: Insights from Rheumatoid arthritis – A five-year follow-up study

“…They also anticipated that homocysteine might not only reflect the inflammatory status in RA patients but also predict the efficacy and adverse reactions of anti-RA therapy (Fujimaki et al 2009). …”

Polimorfismo do gene timidilato sintase e nível plasmático total de homocisteína em um grupo de pacientes turcos com artrite reumatoide: relação com a atividade da doença e toxicidade ao metotrexato

“…5,18 Relatou-se que os níveis de homocisteína plasmática estão relacionados com marcadores inflamatórios em alguns pacientes com AR. 16,17 Isso concorda com os dados encontrados no presente estudo, que indicam uma relação entre o VHS e os níveis de homocisteína nos indivíduos estudados.…”

“…[15][16][17] Cada vez mais estudos de farmacogenética mostram que diversos polimorfismos de genes, incluindo a variante TS-5' UTR 3R/2R, resultam em hiper-homocisteinemia, que poderia ser responsável pelos efeitos adversos mais comuns e graves relacionados com o MTX. 7,17,18 Além disso, a hiper-homocisteinemia tem sido associada à inflamação na AR.…”

“…Também se sabe que os níveis de homocisteína são influenciados por nutrientes, como o ácido fólico e vitaminas do complexo B, e fármacos antirreumáticos, como o MTX. 6,7,16 Os objetivos deste estudo foram determinar a frequência de polimorfismos de repetição dupla/tripla (2R/3R) do gene TS e …”