Sara Remuzgo-Martínez1, Fernanda Genre1, Raquel López-Mejías1, Begoña Ubilla1, Veronica Mijares1, Trinitario Pina1, Alfonso Corrales1, Ricardo Blanco1, Javier Martín2, Javier Llorca3, Miguel Á González-Gay4. 1. Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain. 2. Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Granada, Spain. 3. Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), IDIVAL, Santander, Spain. 4. Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain. miguelaggay@hotmail.com.
Abstract
OBJECTIVES: Impairment of methylene tetrahydrofolate reductase (MTHFR), a key enzyme in the folate metabolism, results in an elevated plasma level of homocysteine, considered an independent risk factor for cardiovascular (CV) disease. Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased risk of CV death. Polymorphisms in the MTHFR gene increase the frequency of CV disease in RA. The aim of this study was to determine the expression of MTHFR gene in patients with RA, with and without ischaemic heart disease (IHD). METHODS: Relative expression of MTHFR gene and beta-actin and GAPDH as housekeeping genes was quantified by quantitative real-time polymerase chain reaction. It was analysed by the comparative Ct (threshold cycle) method in peripheral blood from 26 Spanish patients with RA (12 with IHD and 14 without IHD) and 10 healthy controls. MTHFR expression level in RA patients was also assessed according to disease activity, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies status. RESULTS: MTHFR expression was significantly reduced in patients with RA compared to controls (fold change = 0.85, p=0.029). It was especially true for RA patients with IHD (fold change= 0.79, p=0.021). However, no statistically significant relationship between MTHFR expression level in patients with RA and DAS28 CRP, DAS28 ESR, RF and anti-CCP status was observed. CONCLUSIONS: Patients with RA, in particular those with IHD, show a decreased expression of the MTHFR gene. This may support a potential implication of the transcriptional regulation of MTHFR in the pathogenesis of RA.
OBJECTIVES: Impairment of methylene tetrahydrofolate reductase (MTHFR), a key enzyme in the folate metabolism, results in an elevated plasma level of homocysteine, considered an independent risk factor for cardiovascular (CV) disease. Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased risk of CV death. Polymorphisms in the MTHFR gene increase the frequency of CV disease in RA. The aim of this study was to determine the expression of MTHFR gene in patients with RA, with and without ischaemic heart disease (IHD). METHODS: Relative expression of MTHFR gene and beta-actin and GAPDH as housekeeping genes was quantified by quantitative real-time polymerase chain reaction. It was analysed by the comparative Ct (threshold cycle) method in peripheral blood from 26 Spanish patients with RA (12 with IHD and 14 without IHD) and 10 healthy controls. MTHFR expression level in RApatients was also assessed according to disease activity, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies status. RESULTS:MTHFR expression was significantly reduced in patients with RA compared to controls (fold change = 0.85, p=0.029). It was especially true for RApatients with IHD (fold change= 0.79, p=0.021). However, no statistically significant relationship between MTHFR expression level in patients with RA and DAS28 CRP, DAS28 ESR, RF and anti-CCP status was observed. CONCLUSIONS:Patients with RA, in particular those with IHD, show a decreased expression of the MTHFR gene. This may support a potential implication of the transcriptional regulation of MTHFR in the pathogenesis of RA.
Authors: Sara Remuzgo-Martínez; Fernanda Genre; Santos Castañeda; Alfonso Corrales; Pablo Moreno-Fresneda; Begoña Ubilla; Verónica Mijares; Virginia Portilla; Jesús González-Vela; Trinitario Pina; Gonzalo Ocejo-Vinyals; Juan Irure-Ventura; Ricardo Blanco; Javier Martín; Javier Llorca; Raquel López-Mejías; Miguel A González-Gay Journal: Sci Rep Date: 2017-09-05 Impact factor: 4.379
Authors: Mirna Gisel González-Mercado; Fernando Rivas; M Patricia Gallegos-Arreola; M Cristina Morán-Moguel; Mario Salazar-Páramo; Laura González-López; J Iván Gámez-Nava; J Francisco Muñoz-Valle; Ricardo Medina-Coss Y León; Anahí González-Mercado; Mario A Aceves; Nory O Dávalos; Agustín Macías-Chumacera; Ingrid P Dávalos Journal: Genet Test Mol Biomarkers Date: 2017-10-10
Authors: Fernanda Genre; Javier Rueda-Gotor; Sara Remuzgo-Martínez; Verónica Pulito-Cueto; Alfonso Corrales; Verónica Mijares; Leticia Lera-Gómez; Virginia Portilla; Rosa Expósito; Cristina Mata; Ricardo Blanco; Javier Llorca; Vanesa Hernández-Hernández; Esther Vicente; Cristina Fernández-Carballido; María Paz Martínez-Vidal; David Castro-Corredor; Joaquín Anino-Fernández; Carlos Rodríguez-Lozano; Oreste Gualillo; Juan Carlos Quevedo-Abeledo; Santos Castañeda; Iván Ferraz-Amaro; Raquel López-Mejías; Miguel Á González-Gay Journal: Sci Rep Date: 2020-06-15 Impact factor: 4.379