RESUMEN
Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real-life clinical practice. Ninety patients with plaque psoriasis recruited from-Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI ≤1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI ≤1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI ≤1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to -0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real-world practice conditions.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Femenino , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto , Polimorfismo de Nucleótido Simple , Resultado del Tratamiento , Genotipo , Anciano , Polimorfismo GenéticoRESUMEN
BACKGROUND: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. OBJECTIVE: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. METHODS: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. RESULTS: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. CONCLUSION: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Polimorfismo de Nucleótido Simple , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Femenino , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Persona de Mediana Edad , Adulto , Fármacos Dermatológicos/uso terapéutico , MicroARNs/genética , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines.
Asunto(s)
Capecitabina/uso terapéutico , Dihidrouracilo Deshidrogenasa (NADP)/genética , Fluorouracilo/uso terapéutico , Técnicas de Genotipaje/normas , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Selección de Paciente , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Epigenetics is the study of the mechanisms that regulate gene expression without modifying DNA sequences. Knowledge of and evidence about how epigenetics plays a causative role in the pathogenesis of many skin diseases is increasing. Since the epigenetic changes present in tumor diseases have been thoroughly reviewed, we believe that knowledge of the new epigenetic findings in non-tumor immune-mediated dermatological diseases should be of interest to the general dermatologist. Hence, the purpose of this review is to summarize the recent literature on epigenetics in most non-tumor dermatological pathologies, focusing on psoriasis. Hyper- and hypomethylation of DNA methyltransferases and methyl-DNA binding domain proteins are the most common and studied methylation mechanisms. The acetylation and methylation of histones H3 and H4 are the most frequent and well-characterized histone modifications and may be associated with disease severity parameters and serve as therapeutic response markers. Many specific microRNAs dysregulated in non-tumor dermatological disease have been reviewed. Deepening the study of how epigenetic mechanisms influence non-tumor immune-mediated dermatological diseases might help us better understand the role of interactions between the environment and the genome in the physiopathogenesis of these diseases.
Asunto(s)
Epigénesis Genética , Epigenómica , Predisposición Genética a la Enfermedad , Enfermedades de la Piel/genética , Metilación de ADN/genética , Regulación de la Expresión Génica/inmunología , Histonas/genética , Humanos , MicroARNs/genética , Psoriasis/genética , Psoriasis/inmunología , Psoriasis/patología , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/patologíaAsunto(s)
Artritis Psoriásica/tratamiento farmacológico , Variantes Farmacogenómicas , Factor de Necrosis Tumoral alfa/genética , Proteínas Adaptadoras Transductoras de Señales , Adulto , Proteínas de Unión al ADN/genética , Resistencia a Medicamentos/efectos de los fármacos , Humanos , Persona de Mediana Edad , Dimensión del Dolor , Pruebas de Farmacogenómica , Polimorfismo de Nucleótido Simple , Calidad de Vida , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Receptores Tipo II del Factor de Necrosis Tumoral/genética , Índice de Severidad de la Enfermedad , Péptidos y Proteínas Asociados a Receptores de Factores de Necrosis Tumoral/genética , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Anti-tumor necrosis factor (anti-TNF) drugs are effective against psoriasis, although 20-30% of patients are nonresponders. Few pharmacogenomic studies have been performed to predict the response to anti-TNF drugs in psoriasis. We studied 173 polymorphisms to establish an association with the response to anti-TNF drugs in patients with moderate-to-severe plaque psoriasis (N=144). We evaluated the response using PASI75 at 3, 6 and 12 months. The results of the multivariate analysis showed an association between polymorphisms in PGLYR4, ZNF816A, CTNNA2, IL12B, MAP3K1 and HLA-C genes and the response at 3 months. Besides, the results for polymorphisms in IL12B and MAP3K1 were replicated at 6 months. We also obtained significant results for IL12B polymorphism at 1 year. Moreover, polymorphisms in FCGR2A, HTR2A and CDKAL1 were significant at 6 months. This is the first study to show an association with these polymorphisms. However, these biomarkers should be validated in large-scale studies before implementation in clinical practice.
Asunto(s)
Fármacos Dermatológicos/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Biomarcadores/metabolismo , Femenino , Genotipo , Humanos , Masculino , Farmacogenética/métodos , Psoriasis/metabolismoRESUMEN
Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months. All of the patients were Caucasian, older than 18 years old, with chronic plaque Psor, and had completed at least 24 weeks of anti-TNF therapy (adalimumab, etanercept or infliximab). The treatment response to anti-TNF agents was evaluated according to the achievement of PASI50 and PASI75 at weeks 12 and 24. Those who achieved PASI75 at week 24 were considered good responders. All patients were genotyped for the selected single-nucleotide polymorphisms (SNPs) at IL17RA gene. A total of 238 patients were included (57% male, mean age 46 years). One hundred and five patients received adalimumab, 91 patients etanercept and 42 infliximab. The rs4819554 promoter SNP allele A was significantly more common among responders at weeks 12 (P=0.01) and 24 (P=0.04). We found a higher frequency of AA versus AG+GG among responders, but the difference was only significant at week 12 (P=0.03, odd ratio=1.86, 95% confidence of interval=1.05-3.27). Thus, in the study population, the SNP rs4819554 in the promoter region of IL17RA significantly influences the response to anti-TNF drugs at week 12.
Asunto(s)
Polimorfismo de Nucleótido Simple/genética , Psoriasis/genética , Receptores de Interleucina-17/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/uso terapéutico , Alelos , Estudios Transversales , Etanercept/uso terapéutico , Femenino , Genotipo , Humanos , Infliximab/uso terapéutico , Interleucina-17/genética , Masculino , Persona de Mediana Edad , Psoriasis/tratamiento farmacológicoAsunto(s)
Fármacos Dermatológicos/uso terapéutico , Psoriasis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/uso terapéutico , Biomarcadores/metabolismo , Epigénesis Genética/fisiología , Etanercept/uso terapéutico , Femenino , Humanos , Infliximab/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Paradoxical psoriasiform reactions to anti-tumor necrosis factor α (TNFα) agents have been described. We aimed to study the association between these reactions and polymorphisms in genes previously associated with psoriasis or other autoimmune diseases. A total of 161 patients with plaque-type psoriasis treated with anti-TNFα drugs were genotyped for 173 single-nucleotide polymorphisms (SNPs) using the Illumina Veracode genotyping platform. Among the 161 patients, 25 patients developed a paradoxical psoriasiform reaction consisting of a change in morphology, mostly to guttate psoriasis (88%). These lesions developed 9.20±13.52 months after initiating treatment, mainly with etanercept (72%). Psoriasis type and a Psoriasis Area and Severity Index (PASI) 75 response to treatment were not associated with lesions. Multivariate logistic regression revealed that five SNPs (rs11209026 in IL23R, rs10782001 in FBXL19, rs3087243 in CTLA4, rs651630 in SLC12A8 and rs1800453 in TAP1) were associated with paradoxical reactions. This is the first study to show an association between genetic polymorphisms and paradoxical reactions in patients with psoriasis treated with anti-TNFα drugs.The Pharmacogenomics Journal advance online publication, 21 July 2015; doi:10.1038/tpj.2015.53.
Asunto(s)
Fármacos Dermatológicos/efectos adversos , Erupciones por Medicamentos/genética , Variantes Farmacogenómicas/genética , Polimorfismo de Nucleótido Simple , Psoriasis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Transportador de Casetes de Unión a ATP, Subfamilia B, Miembro 2/genética , Adulto , Anciano , Antígeno CTLA-4/genética , Proteínas de Unión al ADN/genética , Erupciones por Medicamentos/diagnóstico , Proteínas F-Box/genética , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Pruebas de Farmacogenómica , Fenotipo , Valor Predictivo de las Pruebas , Psoriasis/inmunología , Receptores de Interleucina/genética , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND/AIMS: To evaluate the incidence rate of relapse in patients with inflammatory bowel disease (IBD) undergoing chondroitin sulphate (CS) treatment and its effect on the concentrations of several pro-inflammatory proteins. METHODS: Prospective, observational, 12-month follow-up study in patients with IBD in remission, starting CS (Condrosan®, Bioiberica S.A.) treatment for osteoarthritis (OA). Crohn's Disease Activity Index and modified Truelove-Witts severity index were calculated for Crohn's disease and ulcerative colitis (UC) respectively. Levels of vascular endothelial growth factor (VEGFA), -C, fibroblast growth factor 2, hepatocyte growth factor, angiopoietin (Ang)-1, Ang-2, transforming growth factor beta, tumour necrosis factor alpha, interleukin (IL)-1ß, IL-6, IL-12, IL-17, IL-23, intracellular adhesion molecule-1, vascular adhesion molecule-1, matrix metalloproteinase-3 and PGE2 were quantified by ELISA. OA joint pain was evaluated using a visual analogue scale. RESULTS: A total of 37 patients (19 UC and 18 Crohn's disease) were included. The mean values for OA joint pain decreased after 12 months from 5.9 ± 2.8 to 3.0 ± 2.3 (p < 0.05). Only 1 patient (with UC) flared during follow-up. The incidence rate of relapse was 3.4% per patient-year of follow-up. Mean serum VEGFA levels increased between baseline (492 pg/ml) and 12-month treatment (799 pg/ml; p < 0.05). CONCLUSION: The incidence of IBD relapse in patients under CS treatment was lower than that generally reported. This treatment might modulate VEGFA. CS decreases OA-related pain in patients with IBD.
Asunto(s)
Sulfatos de Condroitina/uso terapéutico , Mediadores de Inflamación/sangre , Enfermedades Inflamatorias del Intestino/sangre , Péptidos y Proteínas de Señalización Intercelular/sangre , Osteoartritis/tratamiento farmacológico , Anciano , Artralgia/etiología , Femenino , Estudios de Seguimiento , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/patología , Masculino , Persona de Mediana Edad , Osteoartritis/complicaciones , Osteoartritis/patología , Dimensión del Dolor , Estudios Prospectivos , Recurrencia , Índice de Severidad de la Enfermedad , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular/sangreAsunto(s)
Polimorfismo de Nucleótido Simple/genética , Psoriasis/genética , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Antígenos HLA-C/genética , Antígenos HLA-C/inmunología , Humanos , Sistema Inmunológico/fisiología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/inmunología , Psoriasis/inmunología , Factores de RiesgoRESUMEN
BACKGROUND: Antitumour necrosis factor (anti-TNF)-α agents can be used successfully to treat patients with psoriasis and other inflammatory diseases. However, very few studies have examined the relationship between TNF-α polymorphisms and the response to anti-TNF-α agents. OBJECTIVES: To study the association of single nucleotide polymorphisms (SNPs) of the TNF-α promoter and IL12B/IL23R genes with the response to anti-TNF-α in patients with psoriasis. METHODS: SNPs for the TNF-α promoter and IL12B/IL23R genes, and the presence of the HLA-Cw6 haplotype were genotyped for 109 patients. We studied the association between these SNPs and the efficacy of treatment at 3 and 6 months [Psoriasis Area and Severity Index (PASI) and body surface area (BSA)]. RESULTS: Patients with the TNF-α-238GG genotype more frequently achieved a PASI75 at 6 months (82·5% vs. 58·8%, P = 0·049). At 6 months, patients with the TNF-α-857CT/TT genotypes showed greater improvements in PASI score and BSA (83·1% vs. 92·7%, P = 0·004; 82·7% vs. 92·6%, P = 0·009) and more frequently achieved PASI75 (71·4% vs. 96·3%, P = 0·006). More patients with the TNF-α-1031TT genotype achieved PASI75 at 3 months (90·8 vs. 75·7, P = 0·047) and 6 months (85·5% vs. 65·7%, P = 0·038) and demonstrated superior improvements in PASI at 6 months (89·9% vs. 78·7%, P = 0·041). Patients with the IL23R-GG genotype (rs11209026) achieved PASI90 at 6 months more frequently (66·3% vs. 0, P = 0·006) and the improvement of the PASI score was also greater (86·8% vs. 67·8%, P = 0·013). Patients with the HLA-Cw6 haplotype showed poorer response than those without this haplotype. CONCLUSION: This study identified a relationship between certain TNF-α and IL12B/IL23R polymorphisms and the short-term response to anti-TNF-α drugs. If these results are confirmed, this information will allow for stratified consent with more accurate prediction of response/personalized choice of treatment hierarchy for the patient.
Asunto(s)
Polimorfismo de Nucleótido Simple/genética , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Receptores de Interleucina-12/genética , Receptores de Interleucina/genética , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Adulto , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Estudios de Casos y Controles , Fármacos Dermatológicos/uso terapéutico , Etanercept , Femenino , Genotipo , Humanos , Inmunoglobulina G/uso terapéutico , Infliximab , Masculino , Regiones Promotoras Genéticas/genética , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Psoriasis (Ps) is a chronic inflammatory disease with an important genetic component. It shares pathophysiological mechanisms with other autoimmune diseases such as psoriatic arthritis (PsA), rheumatoid arthritis (RA) and Crohn's disease (CD). These conditions can be treated using biological drugs such as infliximab, adalimumab and etanercept, which selectively block the proinflammatory cytokine tumor necrosis factor (TNF)-α. Although these agents have greatly improved the prognosis of Ps, PsA, RA and CD, they do not cure the disease and are expensive; in addition, significant proportions of patients do not respond or develop serious adverse effects. Therefore, it is important to investigate biomarkers, such as gene polymorphisms, that can predict which patients will respond best to a specific drug. Some polymorphisms in genes TNF, TNF receptor superfamily 1B (TNFR1B) and TNFα-induced protein 3 gene (TNFAIP3) have been associated with response to anti-TNF therapy in patients with Ps. The present article reviews other polymorphisms that could also play a role in prediction of response to these treatments.
Asunto(s)
Artritis Psoriásica/genética , Artritis Reumatoide/genética , Enfermedad de Crohn/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/genética , Adalimumab , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Artritis Psoriásica/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores Farmacológicos , Enfermedad de Crohn/genética , Humanos , Infliximab , Polimorfismo Genético , Pronóstico , Psoriasis/genética , Psoriasis/fisiopatología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
In bioequivalence studies, intra-individual variability (CV(w)) is critical in determining sample size. In particular, highly variable drugs may require enrollment of a greater number of subjects. We hypothesize that a strategy to reduce pharmacokinetic CV(w), and hence sample size and costs, would be to include subjects with decreased metabolic enzyme capacity for the drug under study. Therefore, two mirtazapine studies, two-way, two-period crossover design (n=68) were re-analysed to calculate the total CV(w) and the CV(w)s in three different CYP2D6 genotype groups (0, 1 and ≥ 2 active genes). The results showed that a 29.2 or 15.3% sample size reduction would have been possible if the recruitment had been of individuals carrying just 0 or 0 plus 1 CYP2D6 active genes, due to the lower CV(w). This suggests that there may be a role for pharmacogenetics in the design of bioequivalence studies to reduce sample size and costs, thus introducing a new paradigm for the biopharmaceutical evaluation of drug products.
Asunto(s)
Antidepresivos Tricíclicos/administración & dosificación , Antidepresivos Tricíclicos/farmacocinética , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Mianserina/análogos & derivados , Estudios Cruzados , Femenino , Genotipo , Voluntarios Sanos , Humanos , Masculino , Mianserina/administración & dosificación , Mianserina/farmacocinética , Mirtazapina , Farmacogenética/métodos , Tamaño de la Muestra , Equivalencia TerapéuticaRESUMEN
Risperidone non-compliance is often high due to undesirable side effects, whose development is in part genetically determined. Studies with genetic variants involved in the pharmacokinetics and pharmacodynamics of risperidone have yielded inconsistent results. Thus, the aim of this study was to investigate the putative association of genetic markers with the occurrence of four frequently observed adverse events secondary to risperidone treatment: sleepiness, weight gain, extrapyramidal symptoms and sexual adverse events. A series of 111 schizophrenia inpatients were genotyped for genetic variants previously associated with or potentially involved in risperidone response. Presence of adverse events was the main variable and potential confounding factors were considered. Allele 16Gly of ADRB2 was significantly associated with a higher risk of sexual adverse events. There were other non-significant trends for DRD3 9Gly and SLC6A4 S alleles. Our results, although preliminary, provide new candidate variants of potential use in risperidone safety prediction.
Asunto(s)
Estudios de Asociación Genética , Receptores Adrenérgicos beta 2/genética , Risperidona/efectos adversos , Esquizofrenia/genética , Alelos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/inducido químicamente , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Humanos , Polimorfismo de Nucleótido Simple , Receptores de Dopamina D3/genética , Risperidona/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/patología , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genéticaRESUMEN
Introducción: En diversos estudios se ha descrito la asociación de los polimorfismos del factor de necrosis tumoral α (TNF-Alfa) y patologías inflamatorias como la psoriasis vulgar y la artritis psoriásica, aunque los resultados son variables según la población de origen de la muestra. No se han realizado estudios previamente en población española. Objetivo: Analizar los polimorfismos de la región promotora del gen del TNF-Alfa en pacientes con psoriasis moderada-grave y establecer las posibles diferencias genotípicas con los hallados en un grupo de voluntarios sanos. Material y métodos: Se seleccionaron 89 pacientes con psoriasis moderada-grave y 76 controles sin antecedentes familiares ni personales de psoriasis. Se genotiparon los polimorfismos de la región promotora del gen del TNF-Alfa en ambos grupos. Resultados: Observamos una mayor prevalencia de genotipo con ambos alelos en estado silvestre en posición -238 (GG, 86,5% vs 70,4% respectivamente) y -1031 (TT, 80,2% vs 45,8% respectivamente) en el grupo de pacientes con psoriasis al compararlo con el grupo control. Las diferencias halladas en posición -308 y -857 no fueron significativas. Conclusión: Existen diferencias en los polimorfismos en las posiciones -238 y -1031 entre pacientes con psoriasis moderada-grave y voluntarios sanos, lo cual apoya la importancia del papel del TNF-Alfa en la fisiopatología de esta entidad (AU)
Background: Several studies have reported an association between tumor necrosis factor α (TNF-Alfa) polymorphisms and inflammatory diseases such as psoriasis vulgaris and psoriatic arthritis, although the results vary according to the population studied. No studies have been performed in the Spanish population. Objective: To analyze the polymorphisms of the promoter region of the TNF-Alfa gene in patients with moderate to severe psorasis and to identify potential differences in genotype compared to a group of healthy volunteers. Material and methods: Eighty-nine patients with moderate to severe psoriasis and 76 healthy controls with no personal or family history of psoriasis were selected. Polymorphisms of the TNF-Alfa promoter region of both groups were genotyped. Results: We observed a higher prevalence of the genotype with both wild-type alleles at positions -238 (GG genotype, 86.5% vs 70.4%, respectively) and -1031 (TT genotype, 80.2% vs 45.8%, respectively) in patients compared to the healthy control group. The differences at positions -308 and -857 were not significant. Conclusion: There are differences in polymorphisms at positions -238 and -1031 in patients with moderate to severe psoriasis compared to healthy volunteers. This observation provides further support for the importance of the part that TNF-Alfa plays in the pathophysiology of this disease (AU)
Asunto(s)
Humanos , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/genética , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Farmacogenética/tendencias , Polimorfismo Genético/genética , Polimorfismo Genético/fisiología , Reacción en Cadena de la Polimerasa/instrumentación , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: Several studies have reported an association between tumor necrosis factor α (TNF-α) polymorphisms and inflammatory diseases such as psoriasis vulgaris and psoriatic arthritis, although the results vary according to the population studied. No studies have been performed in the Spanish population. OBJECTIVE: To analyze the polymorphisms of the promoter region of the TNF-α gene in patients with moderate to severe psorasis and to identify potential differences in genotype compared to a group of healthy volunteers. MATERIAL AND METHODS: Eighty-nine patients with moderate to severe psoriasis and 76 healthy controls with no personal or family history of psoriasis were selected. Polymorphisms of the TNF-α promoter region of both groups were genotyped. RESULTS: We observed a higher prevalence of the genotype with both wild-type alleles at positions -238 (GG genotype, 86.5% vs 70.4%, respectively) and -1031 (TT genotype, 80.2% vs 45.8%, respectively) in patients compared to the healthy control group. The differences at positions -308 and -857 were not significant. CONCLUSION: There are differences in polymorphisms at positions -238 and -1031 in patients with moderate to severe psoriasis compared to healthy volunteers. This observation provides further support for the importance of the part that TNF-α plays in the pathophysiology of this disease.
Asunto(s)
Polimorfismo Genético , Psoriasis/genética , Factor de Necrosis Tumoral alfa/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , España , Adulto JovenRESUMEN
Chronic hepatitis C (CHC) is a worldwide health problem that is highly related to liver fibrosis, cirrhosis, and hepatocellular carcinoma. The achievement of response to the current standard of care-pegylated interferon plus ribavirin-has recently been described to be associated with single-nucleotide polymorphisms (SNPs) near the IL-28B gene. Additionally, baseline expression levels of genes involved in interferon (IFN)-stimulated genes (ISGs) have been found to be related to treatment outcome. In the present study, 285 patients were genotyped for 63 SNPs within genes of the IFN signaling pathway (IPGs) and ISGs. Two ISG polymorphisms-OASL rs12819210 (odds ratio (OR)=2.1, P=0.03) and IFIT1 rs304478 (OR=2.5, P=0.01)-were found to be independent predictive factors of sustained virological response (SVR) after adjusting for other clinical covariates. Furthermore, the predictive value of IL-28B SNP was notably improved by simultaneous genotyping of rs12819210 and rs304478, particularly in patients with the worst prognosis (viral genotype 1, area under the curve (AUC)=0.74). In conclusion, ISG SNPs could constitute a valuable tool for individualizing CHC therapy.