RESUMEN
Sarcoidosis is included within the multisystemic granulomatous diseases with autoimmune character. The case of a 51-year-old man with hemoptysis, cholestasis and bone lesions is presented. After ruling out infectious, inflammatory and neoplastic entities, a diagnosis of sarcoidosis and autoimmune hepatitis with primary biliary cholangitis was established.
Asunto(s)
Colangitis , Colestasis , Hepatitis Autoinmune , Cirrosis Hepática Biliar , Sarcoidosis , Masculino , Humanos , Persona de Mediana Edad , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática Biliar/diagnóstico , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico por imagen , Colestasis/complicaciones , Hepatitis Autoinmune/complicaciones , Granuloma , Colangitis/complicacionesRESUMEN
OBJECTIVES: The functional variant R620W of the protein tyrosine phosphatase non receptor-22 (PTPN22) gene plays an important role in susceptibility to several immuno-mediated pathologies. Behçet's disease (BD) is a complex disease related to the immune system with a demonstrated genetic base. The HLA class I genes are the most important genetic factors in BD although other genes are also involved in the susceptibility to this disease. The PTPN22 has been proposed as a candidate gene in BD but this association has not been clearly demonstrated yet. The aim of this study was to assess the association of PTPN22 with BD. METHODS: A cohort composed of 404 Spanish BD patients and 1517 unrelated healthy individuals ethnically matched was genotyped in rs2476601 (R620W). Five tag SNPs: rs1217412, rs2476599, rs3789607, rs3765598 and rs1217419 (spanning a 57 Kb region between 3'UTR and 5'UTR) and rs2488457 (located at the promoter region) were also studied in order to perform a screening of the complete gene. Genotyping was performed using TaqMan® assays. The rs2476601 data were included in a meta-analysis together with those published till the date. The rest of SNPs were used in a case-control study. RESULTS: No evidence of the association of rs2476601 with BD in the meta-analysis (P = 0.504 in the model of alleles) was found. In the case-control study, no statistically significant differences were observed when comparing the distribution of variants in patients and controls. CONCLUSIONS: Our results do not support a major role of the PTPN22 gene in BD.
Asunto(s)
Síndrome de Behçet/genética , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/enzimología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Estudios de Asociación Genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Masculino , Oportunidad Relativa , Fenotipo , Regiones Promotoras Genéticas , Factores de Riesgo , EspañaRESUMEN
OBJECTIVES: Behçet's disease (BD) is an immune-mediated and complex disease which has been associated with HLA class I molecules although other genes such as IL23R and IL10 have also been involved in the susceptibility to BD. Recently, an association of variants of the JAK1 and TNFAIP3 genes with the disease has been reported in the Chinese Han population. The aim of the present work was to asses whether the association described in Asian populations is replicated in Europeans. METHODS: This study includes a total of 1155 Spanish subjects of European origin (372 BD and 783 unrelated healthy individuals). Patients were recruited from different hospitals and controls were collected in the same geographic regions and they matched with patients in age and gender. A total of five SNPs, two in the JAK1 gene: rs2780815 and rs310241 and the other three in the TNFAIP3: rs10499194, rs9494885 and rs610604, were included in this study. The genotyping of these SNPs was performed using a real time PCR system (TaqMan® SNP Genotyping Assays). RESULTS: No statistically significant differences were found when the patient and control groups were compared. The distribution of the risk alleles was similar in patients with and without eye manifestations and in patients with and without HLA-B*51. CONCLUSIONS: The association of variants of the genes JAK1 and the TNFAIP3 with BD which has been described in the Chinese population was not replicated in Europeans.
Asunto(s)
Síndrome de Behçet/genética , Proteínas de Unión al ADN/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Janus Quinasa 1/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple , Población Blanca/genética , Adulto , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/enzimología , Síndrome de Behçet/etnología , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Factores de Riesgo , España/epidemiología , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfaRESUMEN
OBJECTIVES: The aim of this study was to investigate the role of the TLR8, a mediator of innate inflammatory response, in susceptibility to two immune-mediated disorders characterised by dysregulation of the immune response, Crohn's and Behçet's diseases (CD and BD). METHODS: A total of 844 CD, 371 BD patients and 1385 controls were genotyped in 8 tag single nucleotide polymorphisms (tSNPs) in the locus TLR8 (chromosome X). All these tSNPs have a minor allele frequency greater than 0.05 in the Caucasian population. RESULTS: The rs2407992 and the rs5744067 were associated with susceptibility to BD and CD, respectively (OR=1.34, 95%CI=1.10-1.62, p=0.0025 and OR=0.82, 95%CI=0.68-0.99, p=0.045, respectively). Although after stratification by gender, statistically significant differences in the distribution of the aforementioned SNPs were only observed in the females groups (BD OR=1.31, 95%CI=1.06-1.64, p=0.012 and CD OR=0.84, 95%CI=0.72-0.98, p=0.044) the trend was similar among males. Since the rs5744067 and rs2407992 are located in the same linkage disequilibrium block, we performed a haplotypic analysis by combination of the tSNPs. One haplotype (H1) was identified as a protective factor in BD (OR=0.75, 95%CI=0.62-0.90, p=0.0027) and another (H2) as a protective factor in CD (OR=0.78, 95%CI=0.64-094, p=0.0102). No statistically significant differences in the mean of the levels of expression attributable to the haplotype variants were found in the in silico analysis performed. CONCLUSIONS: Our results suggest a relationship between the TLR8 and the susceptibility to CD and BD. Nevertheless, these differences could not be imputed to the levels of expression.
Asunto(s)
Síndrome de Behçet/genética , Enfermedad de Crohn/genética , Haplotipos , Polimorfismo de Nucleótido Simple , Receptor Toll-Like 8/genética , Adulto , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/inmunología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Simulación por Computador , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/inmunología , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , España , Receptor Toll-Like 8/inmunología , Adulto JovenRESUMEN
OBJECTIVES: Behçet's disease (BD) is an immune-mediated and complex disease associated with HLA class I and other genes. The aim of this study was to contribute to a better understanding of the relationship of the 32-bp deletion in the CCR5 gene (CCR5Δ32) and this disease by conducting a case-control study in the Spanish population and also a meta-analysis including all the studies available to date. METHODS: A cohort composed of 348 BD Spanish patients and 477 unrelated healthy and ethnically matched individuals were genotyped in CCR5Δ32 using polymerase chain reaction (PCR) and capillary electrophoresis with fluorescent detection. In the meta-analysis, data from a total of seven populations extracted from four previous studies along with data of the present study were included. RESULTS: Regarding the case-control study, no statistically significant differences were observed when the patient and control groups were compared (allelic model: 0.07 in patients vs. 0.06 in controls, p=0.303). In the meta-analysis, no evidence of association of the CCR5Δ32 polymorphism with BD was observed (pMH=0.091; OR=1.22; 95%CI 0.98 to 1.52 in the allelic model). CONCLUSIONS: The results of this meta-analysis discard a major role of the CCR5Δ32 polymorphism in BD.
Asunto(s)
Síndrome de Behçet/genética , Receptores CCR5/genética , Adulto , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/epidemiología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Medición de Riesgo , Factores de Riesgo , EspañaRESUMEN
Introduction: The knowledge of the aetiology of Behçet disease (BD), an immune-mediated vasculitis, is limited. HLA-B, mainly HLA-B51, and HLA-A molecules are associated with disease, but the ultimate cause of this association remains obscure. There is evidence that NK cells participate in the etiopathology of BD. NK cells have activator and inhibitor surface receptors, like the KIR and the NKG2 families. Classical HLA-class I molecules (A, B and C) are keys in the activity control of the NK because they are KIR ligands. Most NKG2 receptors bind HLA-E, which presents only nonapeptides derived from the signal peptide of other class-I molecules. Objective: This study investigates the contribution of the pair HLA-E and ligand, nonapeptide derived from the 3-11 sequence of the signal peptides of class I classical molecules, to the susceptibility to BD. Methods: We analyzed the frequency of the HLA-derivated nonapeptide forms in 466 BD patients and 444 controls and an HLA-E functional dimorphism in a subgroup of patients and controls. Results: In B51 negative patients, the frequency of VMAPRTLLL was lower (70.4% versus 80.0% in controls; P=0.006, Pc=0.04, OR=0.60, 95%CI 0.41-0.86), and the frequency of VMAPRTLVL was higher (81.6% versus 71.4% in controls; P=0.004, Pc=0.03, OR=1.78, 95%CI 1.20-2.63). In homozygosity, VMAPRTLLL is protective, and VMAPRTLVL confers risk. The heterozygous condition is neutral. There were no significant differences in the distribution of the HLA-E dimorphism. Discussion: Our results explain the association of BD with diverse HLA-A molecules, reinforce the hypothesis of the involvement of the NK cells in the disease and do not suggest a significant contribution of the HLA-E polymorphism to disease susceptibility.
Asunto(s)
Síndrome de Behçet , Arteritis de Células Gigantes , Granulomatosis con Poliangitis , Humanos , Síndrome de Behçet/genética , Antígenos HLA-A , Antígenos HLA-ERESUMEN
OBJECTIVES: To study the bone mass in patients with scleroderma (SSc) from two different Spanish regions and to evaluate the prevalence of vitamin D deficiency and insufficiency in this population and its possible relation to bone mineral density (BMD). METHODS: Disease, bone mineral density related variables and vitamin D were collected from all patients. Statistical analysis was carried out using the SPSS 17 statistics software for Windows. A p<0.05 was considered significant. RESULTS: A Z-score <-1 was found in 21.9% of the control population and 43% of SSc patients. The prevalence of osteopenia/osteoporosis was 50% in the control population and 77% in SSc (p<0.0001). We did not find differences between the prevalence of low BMD in the south (79%) and in the north of Spain (76.3%); but patients from the north had lower levels of vitamin D (27.4±16.2 ng/dL vs. 20.7±11.0 ng/dl; p<0.031). Low levels of vitamin D (<30ng/ml) were found in 69 patients out of 90, ten of them with insufficiency (<10ng/ml). Eighty-four point six percent of the patients with low levels of vitamin D (<30ng/ml) had LBMD compared whith 66.7% of those with normal levels (p=0.073). CONCLUSIONS: The prevalence of osteoporosis/osteopenia in Spanish patient with SSc is very high. Although there are a high prevelence of vitamin D deficiency, we could not demonstrate a relationship of vitamin D deficiency with low mineral density.
Asunto(s)
Densidad Ósea , Enfermedades Óseas Metabólicas/epidemiología , Osteoporosis/epidemiología , Esclerodermia Sistémica/epidemiología , Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Adulto , Anciano , Biomarcadores/sangre , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Estudios Transversales , Femenino , Cuello Femoral/diagnóstico por imagen , Humanos , Modelos Lineales , Modelos Logísticos , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Análisis Multivariante , Osteoporosis/sangre , Osteoporosis/diagnóstico por imagen , Prevalencia , Radiografía , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/diagnóstico por imagen , España/epidemiología , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/diagnóstico por imagenAsunto(s)
Síndrome de Behçet/genética , Proteínas de Unión al GTP/genética , Antígenos HLA-B/genética , Antígeno HLA-B51/genética , Población Blanca/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , GTP Fosfohidrolasas/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Behçet's disease (BD) is an immune-mediated systemic disorder with a well-established genetic base. In a previous study, using a next generation sequencing approach, we found many rare variants and some functional polymorphisms in genes related to autoinflammatory syndromes (AID): CECR1, MEFV, MVK, NLRP3, NOD2, PSTPIP1 and TNFRSF1A in our BD cohort. Our strategy did not allow us to establish either number of patients with variants, proportion of individuals accumulating them or relationship with other genetic factors. With the goal to answer these questions, the individual samples were sequenced. Additionally, three functional polymorphisms: NLRP3 p.Gln703Lys, NOD2 p.Arg702Trp and p.Val955Ile were genotyped using TaqMan assays. A total of 98 patients (27.6%) carried at least one rare variant and 13 of them (3.7%) accumulated two or three. Functional regression model analysis suggests epistatic interaction between B51 and MEFV (P = 0.003). A suggestive protective association of the minor allele of NOD2 p.Arg702Trp (P = 0.01) was found in both, B51 positive and negative individuals. Therefore, a high percentage of patients with BD have rare variants in AID genes. Our results suggest that the association of MEFV with BD could be modulated by the HLA molecules; whereas the protective effect of NOD2 p.Arg702Trp would be independent of HLA.
Asunto(s)
Síndrome de Behçet/patología , Epistasis Genética , Predisposición Genética a la Enfermedad , Antígenos HLA-B/genética , Enfermedades Autoinflamatorias Hereditarias/genética , Mediadores de Inflamación/metabolismo , Polimorfismo Genético , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Síndrome de Behçet/genética , Estudios de Cohortes , Proteínas del Citoesqueleto/genética , Femenino , Genotipo , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Pirina/genética , Receptores Tipo I de Factores de Necrosis Tumoral/genéticaRESUMEN
Behçet's disease (BD) is an immune-mediated vasculitis related to imbalances between the innate and adaptive immune response. Infectious agents or environmental factors may trigger the disease in genetically predisposed individuals. HLA-B51 is the genetic factor stronger associated with the disease, although the bases of this association remain elusive. NK cells have also been implicated in the etiopathogenesis of BD. A family of NK receptors, Killer-cell Immunoglobulin-like Receptor (KIR), with a very complex organization, is very important in the education and control of the NK cells by the union to their ligands, most of them, HLA class I molecules. This study aimed to investigate the contribution of certain KIR functional polymorphisms to the susceptibility to BD. A total of 466 BD patients and 444 healthy individuals were genotyped in HLA class I (A, B, and C). The set of KIR genes and the functional variants of KIR3DL1/DS1 and KIR2DS4 were also determined. Frequency of KIR3DL1*004 was lower in patients than in controls (0.15 vs. 0.20, P = 0.005, Pc = 0.015; OR = 0.70; 95% CI 0.54-0.90) in both B51 positive and negative individuals. KIR3DL1*004, which encodes a misfolded protein, is included in a common telomeric haplotype with only one functional KIR gene, KIR3DL2. Both, KIR3DL1 and KIR3DL2 sense pathogen-associated molecular patterns but they have different capacities to eliminate them. The education of the NK cells depending on the HLA, the balance of KIR3DL1/KIR3DL2 licensed NK cells and the different capacities of these receptors to eliminate pathogens could be involved in the etiopathogenesis of BD.
Asunto(s)
Síndrome de Behçet/diagnóstico , Síndrome de Behçet/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Receptores KIR3DL1/genética , Alelos , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética/métodos , Genotipo , Antígenos HLA/genética , Antígenos HLA/inmunología , Humanos , Masculino , Oportunidad Relativa , Receptores KIR/genéticaRESUMEN
Behçet's disease (BD) is an immune-mediated systemic disorder with a well-established association with HLA class I and other genes. BD has clinical overlap with many autoinflammatory diseases (AIDs). The aim of this study was to investigate the role of rare variants in seven genes involved in AIDs: CECR1, MEFV, MVK, NLRP3, NOD2, PSTPIP1 and TNFRSF1A using a next generation sequencing (NGS) approach in 355 BD patients. To check global association of each gene, 4 tests: SKAT, CollapseBt, C(α) and weighted KBAC were used. Databases: 1000 Genomes Project Phase 3, Infevers, HGMD and ClinVar and algorithms: PolyPhen2 and SIFT were consulted to collect information of the 62 variants found. All the genes resulted associated using SKAT but only 3 (MVK, NOD2 and PSTPIP1) with C(α) and weighted KBAC. When all the genes are considered, 40 variants were associated to AIDs in clinical databases and 25 were predicted as pathogenic at least by one of the algorithms. Including only MVK, NOD2 and PSTPIP1, the associated to AIDs variants found in BD were 20 and the predicted as pathogenic, 12. The maxima contribution corresponds to NOD2. This study supports influence of rare variants in genes involved in AIDs in the pathogenesis of BD.
Asunto(s)
Síndrome de Behçet/genética , Predisposición Genética a la Enfermedad/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Inflamasomas/genética , Mutación , Proteínas Adaptadoras Transductoras de Señales/genética , Adenosina Desaminasa/genética , Proteínas del Citoesqueleto/genética , Femenino , Humanos , Inflamación/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína Adaptadora de Señalización NOD2/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Pirina/genética , Receptores Tipo I de Factores de Necrosis Tumoral/genéticaRESUMEN
Behcet's disease (BD) is an immuno-mediated vasculitis in which knowledge of its etiology and genetic basis is limited. To improve the current knowledge, a genetic analysis performed with the Immunochip platform was carried out in a population from Spain. A discovery cohort comprising 278 BD cases and 1,517 unaffected controls were genotyped using the Immunochip platform. The validation step was performed on an independent replication cohort composed of 130 BD cases and 600 additional controls. The strongest association signals were observed in the HLA class I region, being HLA-B*51 the highest peak (overall P = 6.82E-32, OR = 3.82). A step-wise conditional logistic regression with classical alleles identified HLA-B*57 and HLA-A*03 as additional independent markers. The amino acid model that best explained the association, includes the position 97 of the HLA-B molecule and the position 66 of the HLA-A. Among the non-HLA loci, the most significant in the discovery analysis were: IL23R (rs10889664: P = 3.81E-12, OR = 2.00), the JRKL/CNTN5 region (rs2848479: P = 5.00E-08, OR = 1.68) and IL12A (rs1874886: P = 6.67E-08, OR = 1.72), which were confirmed in the validation phase (JRKL/CNTN5 rs2848479: P = 3.29E-10, OR = 1.66; IL12A rs1874886: P = 1.62E-08, OR = 1.61). Our results confirm HLA-B*51 as a primary-association marker in predisposition to BD and suggest additional independent signals within the class I region, specifically in the genes HLA-A and HLA-B. Regarding the non-HLA genes, in addition to IL-23R, previously reported in our population; IL12A, described in other populations, was found to be a BD susceptibility factor also in Spaniards; finally, a new associated locus was found in the JRKL/CNTN5 region.
Asunto(s)
Síndrome de Behçet/genética , Contactinas/genética , Predisposición Genética a la Enfermedad , Antígeno HLA-B51/genética , Subunidad p35 de la Interleucina-12/genética , Receptores de Interleucina/genética , Alelos , Síndrome de Behçet/inmunología , Síndrome de Behçet/patología , Estudios de Casos y Controles , Contactinas/inmunología , Frecuencia de los Genes , Sitios Genéticos , Antígeno HLA-A3/genética , Antígeno HLA-A3/inmunología , Antígenos HLA-B/genética , Antígenos HLA-B/inmunología , Antígeno HLA-B51/inmunología , Humanos , Inmunoensayo , Subunidad p35 de la Interleucina-12/inmunología , Modelos Logísticos , Análisis por Micromatrices , Modelos Moleculares , Receptores de Interleucina/inmunología , EspañaRESUMEN
OBJECTIVE: Behçet disease (BD) is a multifactorial disease in which infectious agents have been proposed as triggers in genetically predisposed individuals. The aim of our study was to investigate the role of innate immunity receptors, specifically the nucleic acid sensors, in susceptibility to BD. METHODS: Seventy-four tag single nucleotide polymorphisms (tSNP) selected in 9 candidate genes (DDX58, IFIH1, TLR3, TLR7, TLR8, AIM2, IFI16, ZBP1, and TLR9) were genotyped in 371 patients and 854 controls. Assays of mRNA expression and allele-specific transcript quantification (ASTQ) were performed in 110 and 50 controls, respectively. RESULTS: Patients and controls were genotyped and 2 tSNP (rs6940 in IFI16 and rs855873 in AIM2) were associated with BD. To confirm this association, these tSNP were genotyped in 850 additional controls, and the total cohort was randomly divided into 2 cohorts. The association of these 2 tSNP with the disease remained in both cohorts. One haplotype (rs6940T-rs855873G) was identified as a risk factor (OR 1.41, 95% CI 1.06-1.86, p = 0.015), and another (rs6940A-rs855873A) as a protective factor (OR 0.65, 95% CI 0.47-0.90, p = 0.009). Samples with the risk haplotype had lower IFI16 expression levels than samples with the protective (0.99 ± 0.29 vs 1.23 ± 0.50, p = 0.022). Consistently, in the ASTQ assays performed with the nonsynonymous rs6940 SNP, the risk allele had lower IFI16 expression levels than the protective (p = 0.027). CONCLUSION: Our findings suggest association of IFI16, a cytosolic sensor of dsDNA and mediator of the AIM2 inflammasome-dependent pathway, in susceptibility to BD. Differences genetically determined in the levels of this molecule could be the cause of this association.
Asunto(s)
Síndrome de Behçet/genética , Predisposición Genética a la Enfermedad , Proteínas Nucleares/genética , Fosfoproteínas/genética , Polimorfismo de Nucleótido Simple , ARN Mensajero/genética , Adulto , Alelos , Femenino , Genotipo , Haplotipos , Humanos , Inflamasomas/genética , Masculino , Persona de Mediana Edad , Adulto JovenAsunto(s)
Enfermedades Autoinmunes , Servicios de Información/estadística & datos numéricos , Internet/estadística & datos numéricos , Adulto , Enfermedades Autoinmunes/terapia , Enfermedad Crónica , Intervalos de Confianza , Interpretación Estadística de Datos , Educación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Educación del Paciente como Asunto , Relaciones Médico-Paciente , EspañaRESUMEN
Internet has become a widely used tool by patients seeking information on different diseases. The information regarding lupus patients' Internet use is scarce. This study aims to explore the attitudes and practices of lupus patients in southern Spain, regarding Internet use to find health-related information. A survey was carried out including 150 patients from six Andalusian Hospitals. To search for information, 67.3 % of the patients used Internet. The proportion of female Internet users was higher (69.3 vs 46.2 %), particularly those belonging to a patients' association (81.8 vs 32.7 %), and are regular users of Internet (80.2 vs 44.4 %); 37.5 % thought the information found in the Internet was of little use or not useful at all, and 58 % of the respondents stated that the information found caused them concern while for 27 %, it was a relief. Most patients preferred the information given by their physicians (63.6 %); 33.9 % considered that the information from both sources was complementary, and 2.5 % preferred the information obtained from the Internet. A percentage of 85.3 of the patients would like their physicians to provide them with information on high-quality sites regarding their illness. Lupus patients make frequent use of the Internet to look for information on their disease. Considering this, and because better-informed patients follow more precisely the indications given by the physician, medical staff should collaborate in the development of high-quality sites for the patient to have additional sources of information.
Asunto(s)
Conducta en la Búsqueda de Información , Internet , Lupus Eritematoso Sistémico , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distribución por Sexo , España , Encuestas y CuestionariosRESUMEN
Behçet's disease (BD) is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078) and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987) associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population.
Asunto(s)
Aminopeptidasas/metabolismo , Síndrome de Behçet/epidemiología , Síndrome de Behçet/genética , Epistasis Genética/genética , Antígenos HLA-B/metabolismo , Adulto , Aminopeptidasas/genética , Femenino , Frecuencia de los Genes , Antígenos HLA-B/genética , Haplotipos/genética , Humanos , Modelos Logísticos , Masculino , Antígenos de Histocompatibilidad Menor , Oportunidad Relativa , Polimorfismo de Nucleótido Simple/genética , España/epidemiologíaRESUMEN
INTRODUCTION: According to genome wide association (GWA) studies as well as candidate gene approaches, Behçet's disease (BD) is associated with human leukocyte antigen (HLA)-A and HLA-B gene regions. The HLA-B51 has been consistently associated with the disease, but the role of other HLA class I molecules remains controversial. Recently, variants in non-HLA genes have also been associated with BD. The aims of this study were to further investigate the influence of the HLA region in BD and to explore the relationship with non-HLA genes recently described to be associated in other populations. METHODS: This study included 304 BD patients and 313 ethnically matched controls. HLA-A and HLA-B low resolution typing was carried out by PCR-SSOP Luminex. Eleven tag single nucleotide polymorphisms (SNPs) located outside of the HLA-region, previously described associated with the disease in GWA studies and having a minor allele frequency in Caucasians greater than 0.15 were genotyped using TaqMan assays. Phenotypic and genotypic frequencies were estimated by direct counting and distributions were compared using the χ(2) test. RESULTS: In addition to HLA-B*51, HLA-B*57 was found as a risk factor in BD, whereas, B*35 was found to be protective. Other HLA-A and B specificities were suggestive of association with the disease as risk (A*02 and A*24) or protective factors (A*03 and B*58). Regarding the non-HLA genes, the three SNPs located in IL23R and one of the SNPs in IL10 were found to be significantly associated with susceptibility to BD in our population. CONCLUSION: Different HLA specificities are associated with Behçet's disease in addition to B*51. Other non-HLA genes, such as IL23R and IL-10, play a role in the susceptibility to the disease.