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3. Protein tyrosine phosphatase non-receptor 22 and C-Src tyrosine kinase genes are down-regulated in patients with rheumatoid arthritis

Author

Remuzgo-Martínez, Sara, primary, Genre, Fernanda, additional, Castañeda, Santos, additional, Corrales, Alfonso, additional, Moreno-Fresneda, Pablo, additional, Ubilla, Begoña, additional, Mijares, Verónica, additional, Portilla, Virginia, additional, González-Vela, Jesús, additional, Pina, Trinitario, additional, Ocejo-Vinyals, Gonzalo, additional, Irure-Ventura, Juan, additional, Blanco, Ricardo, additional, Martín, Javier, additional, Llorca, Javier, additional, López-Mejías, Raquel, additional, and González-Gay, Miguel A., additional

Published
2017
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4. Impact of Genetic Variants of ATP Binding Cassette B1, AICAR Transformylase/IMP Cyclohydrolase, Folyl-polyglutamate Synthetase, and Methylenetetrahydrofolate Reductase on Methotrexate Toxicity

Author

Sala-Icardo, Luis, Lamana Domínguez, Amalia, Ortiz, Ana María, García Lorenzo, Elena, Moreno Fresneda, Pablo, García-Vicuña, Rosario, González-Álvaro, Isidoro, Sala-Icardo, Luis, Lamana Domínguez, Amalia, Ortiz, Ana María, García Lorenzo, Elena, Moreno Fresneda, Pablo, García-Vicuña, Rosario, and González-Álvaro, Isidoro

Abstract

Objective: To analyze the effect of single nucleotide polymorphisms (SNPs) with well-known functional impact of methylenetetrahydrofolate reductase (MTHFR; rs1801131 and rs1801133), the membrane transporter ABCB1 (rs1045642), the AICAR transformylase/IMP cyclohydrolase (ATIC; rs2372536) and folyl-polyglutamate synthetase (FPGS; rs1544105), on liver and bone marrow toxicity of methotrexate (MTX). Patients and methods: We analyzed 1415 visits from 350 patients of the PEARL (Princesa Early Arthritis Register Longitudinal) study: (732 with MTX, 683 without MTX). The different SNPs were genotyped using speci c TaqMan probes (Applied Biosystems). Multivariate analyzes were performed using generalized linear models in which the dependent variables were the levels of serum alanine aminotransferase (liver toxicity), leukocytes, platelets or hemoglobin (hematologic toxicity) and adjusted for clinical variables (disease activity, etc.), analytical (renal function, etc.), sociodemographic (age, sex, etc.) and genetic variants of MTHFR, ABCB1, ATIC and FPGS. The effect of these variables on the MTX doses prescribed throughout follow-up was also analyzed through multivariate analysis nested by visit and patient. Results: When taking MTX, those patients carrying the CC genotype of rs1045642 in ABCB1 showed signi cantly higher GPT levels (7.1 2.0 U/L; P < .001). Carrying at least one G allele of rs1544105 in FPGS was associated with lower leukocyte ( 0.67 0.32; 0.038), hemoglobin ( 0.34 0.11 g/dL; P = .002), and platelet ( 11.8 4.7; P = .012) levels. The presence of the G allele of rs1544105 in FPGS, and the T allele of rs1801133 in MTHFR, was signi cantly associated with the use of lower doses of MTX. Discussion: Our data suggest that genotyping functional variants in FGPS and MTHFR enzymes and the transporter ABCB1 could help to identify patients with increased risk of MTX toxicity., Ministerio de Economía y Competitividad (MINECO)/Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III, Depto. de Biología Celular, Fac. de Ciencias Biológicas, TRUE, pub

Published
2017

5. Lower frequency of anti-citrullinated protein antibodies among early arthritis patients with high body mass index.

Author

Moreno-Fresneda P, Triguero-Martínez A, Olivas-Martínez I, Ortiz-Aljaro P, González-Escribano MF, Nuño-Nuño L, Ortiz AM, and González-Álvaro I

Subjects
Autoantibodies, Case-Control Studies, Female, HLA-DRB1 Chains, Humans, Male, Peptides, Cyclic, Anti-Citrullinated Protein Antibodies, Arthritis, Rheumatoid diagnosis, Arthritis, Rheumatoid immunology, Body Mass Index
Abstract

Objectives: To investigate the role of body mass index (BMI) in the phenotypic and genotypic characteristics of early arthritis patients., Methods: We analysed the clinical and laboratory parameters from the baseline visit of patients (670 patients [78.51% women]) included in the PEARL study. The WHO definition for low weight, normal weight, overweight and obesity (BMI <18.5, 18.5-25, 25-30 or ≥30 kg/m2, respectively) was applied. Anticitrullinated protein antibodies (ACPA) were studied by ELISA and HLA-DRB1* were genotyped by sequence speci c oligonucleotide probes. The relationship between BMI classification and other variables was analysed using Kruskall-Wallis, Anova and Chi-Square tests. Then multivariate logistic regression was performed to establish the role of BMI in ACPA positivity and ordered logistic regression to establish its relationship with ACPA level., Results: Among the patients studied, 255 (38.06%) were considered overweight and 136 (20.3%) obese. High BMI patients had significantly more pain perception and disability than normal weight patients, whereas no clear differences in disease activity were observed between high BMI and normal weight patients. ACPA positivity was significantly less frequent in overweight and obese patients compared to normal BMI patients. This information was confirmed by adjusting for smoking habit and the presence of shared epitope., Conclusions: Our data support the theory that high BMI patients suffer more frequently from ACPA-negative RA. Nevertheless, although no disease activity differences were observed, these patients showed higher pain and disability scores since the beginning of disease.

Published
2020

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