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Moya P.,Hospital Of La Santa Creu I Sant Pau | Moya P.,Autonomous University of Barcelona | Salazar J.,Hospital Of La Santa Creu I Sant Pau | Salazar J.,Center for Biomedical Research on Rare Diseases | And 7 more authors.
Pharmacogenomics | Year: 2016

Background: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients. Aim: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX. Patients & methods: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes. Results: We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively). Conclusion: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy. © 2016 Future Medicine Ltd.


Moya P.,Autonomous University of Barcelona | Salazar J.,Hospital Of La Santa Creu I Sant Pau | Arranz M.J.,Fundacio Docencia i Recerca Mutua Terrassa | Diaz-Torne C.,Hospital Of La Santa Creu I Sant Pau | And 4 more authors.
Pharmacogenomics | Year: 2016

BACKGROUND: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients.AIM: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX.PATIENTS & METHODS: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes.RESULTS: We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively).CONCLUSION: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy.


Laura I.N.E.,Fundacio Docencia I Recerca Mutua Terrassa | Pablo Sebastian V.,Hospital Universitari Mu TuaTerrassa | Pablo Sebastian V.,University of Barcelona | Roser F.,Hospital Universitari Mu TuaTerrassa | And 15 more authors.
PLoS ONE | Year: 2014

Background: Higher prevalence of atherosclerosis and higher cardiovascular risk is observed in HIV-infected individuals. The biological mechanisms underlying these processes are unclear. Several studies have implicated genetic variants in the inflammatory genes in cardiovascular disease and in HIV natural course infection. Methods & Findings: In this study we have tested the possible association between genetic variants in several inflammatory genes and asymptomatic cardiovascular disease measured by carotid intima media thickness (cIMT) and atherosclerotic plaque presence as dependent variables in 213 HIV-infected individuals. A total of 101 genetic variants in 25 candidate genes have been genotyped. Results were analyzed using Plink and SPSS statistical packages. We have found several polymorphisms in the genes ALOX5 (rs2115819 p = 0.009), ALOX5AP (rs9578196 p = 0.007; rs4769873 p = 0.004 and rs9315051 p = 0.0004), CX3CL1 (rs4151117 p = 0.040 and rs614230 p = 0.015) and CCL5 (rs3817655 p = 0.018 and rs2107538 p = 0.018) associated with atherosclerotic plaque. cIMT mean has been associated with CRP (1130864 p = 0.0003 and rs1800947 p = 0.008), IL1RN (rs380092 p = 0.002) and ALOX5AP (rs3885907 p = 0.02) genetic variants. Conclusions: In this study we have found modest associations between genetic variants in several inflammatory genes and atherosclerotic plaque or cIMT. Nevertheless, our study adds evidence to the association between inflammatory pathway genetic variants and the atherosclerotic disease in HIV-infected individuals. Copyright: - 2014 Ibá n? ez et al.

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