RESUMEN
Objective: To explore the interaction between family history of diabetes and hyperlipidemia on the risk of diabetes in population with normotension. Methods: A multistage stratified probability random sampling was conducted to select a representative sample of urban residents aged 20-74 years in Harbin. A total of 376 diabetes patients with normotension and 3 692 residents with normal blood pressure, normal fasting glucose, and normal 2 hours glucose from OGTT were surveyed. The interaction was evaluated by using crossover analysis and additive model. Results: Multivariate logistic regression analysis indicated that there was a possible additive interaction between family history of diabetes and hyperlipidemia on the risk of diabetes. The relative excess risk due to the interaction, the attributable proportion due to the interaction, and the synergy index were 1.97 (95%CI:-0.32-4.26), 0.30 (95%CI: 0.03-0.57), and 1.54 (95%CI: 0.96-2.47), respectively. There were significant combination effects between family history of diabetes and high both total cholesterol and triglyceride, isolated high total cholesterol, and isolated high triglyceride levels; the ORs were 10.55 (95%CI: 5.62-19.80), 7.81 (95%CI: 3.65-16.71) and 5.13 (95%CI: 3.22-8.16), respectively. Conclusion: There might be synergistic effect between family history of diabetes and hyperlipidemia on the risk of diabetes in population with normotension.
Asunto(s)
Diabetes Mellitus/epidemiología , Predisposición Genética a la Enfermedad , Hiperlipidemias/epidemiología , Adulto , Anciano , Presión Sanguínea , China/epidemiología , Colesterol , Estudios Transversales , Diabetes Mellitus/etnología , Diabetes Mellitus/genética , Ayuno , Femenino , Humanos , Hiperlipidemias/etnología , Hiperlipidemias/genética , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
This study aimed to investigate the relationship between type I interferon (IFN-I) and plaque stability in pristane-treated apolipoprotein E-knockout (ApoE(-/-)) mice. Antinuclear antibody (ANA) and extractable nuclear antigen antibody (ENA) levels were measured by immunofluorescence and enzyme-linked immunospot assay. Atherosclerotic plaques were detected by Sirius red/fast green staining. Cell apoptosis was detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling. Gene expression was determined by real-time PCR analyses. We found that pristane-treated ApoE(-/-) mice developed a lupus-like syndrome characterized by an increased production of serum ANA and ENA. Pristane treatment decreased the collagen content and increased the number of apoptotic cells in plaques. Moreover, IFN-induced ISG15, IFIT1-1, and IFIT1-2 gene expression was increased in peripheral blood cells and aortic plaques. An IFN-α-stimulated macrophage supernatant inhibited collagen type I, alpha 1 gene expression in vascular smooth muscle cells. We concluded that the vulnerability of plaques was associated with the activation of IFN-I in pristane-treated ApoE(-/-) mice. Thus, we speculated that the higher prevalence of cardiovascular events in patients with systemic lupus erythematosus could be due to plaque instability.
Asunto(s)
Aterosclerosis/genética , Interferón-alfa/genética , Lupus Eritematoso Sistémico/genética , Placa Aterosclerótica/genética , Animales , Apolipoproteínas E/genética , Apoptosis/genética , Aterosclerosis/patología , Modelos Animales de Enfermedad , Humanos , Lupus Eritematoso Sistémico/patología , Macrófagos/patología , Ratones , Ratones Noqueados , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Placa Aterosclerótica/patologíaRESUMEN
OBJECTIVE: To identify disease-related genes and immune-regulatory pathways in the pathogenesis of systemic lupus erythematosus (SLE) by using gene expression profiling and protein-protein interaction analysis. METHODS: Peripheral white blood cell gene expression profiles of 10 SLE patients were determined by oligonucleotide microarray analysis. Clustering of the gene expression profile was compared with the clinical immune phenotype. SLE-induced genes that were over- or under-expressed were determined and independently validated using a real-time polymerase chain reaction (PCR) method. To study their potential function and the possible pathways involved, a candidate gene was cloned and a GST (glutathione S-transferase) fusion protein was expressed in Escherichia coli. The fusion protein was further purified using the glutathione Sepharose 4B system, and was treated as bait to capture prey from SLE peripheral white blood cell lysate. MALDI-TOF (matrix-assisted laser desorption/ionization-time-of-flight) mass spectrometry was then performed to determine the prey protein. RESULTS: Similarity was found between the gene expression profile and the immune phenotype clusters of the SLE patients. More than 20 disease-associated genes were identified, some of which have not been related to SLE previously. Of these genes, a cluster of interferon-induced genes were highly correlated. IFIT1 (interferon-induced with tetratricopeptide repeats 1) was one of these genes, and overexpression of its mRNA was confirmed independently by real-time PCR in a larger population (40 SLE patients and 29 normal controls). An IFIT1 protein- protein interaction study showed that IFIT1 may interact with Rho/Rac guanine nucleotide exchange factor. CONCLUSION: The gene expression profile seems to be the molecular basis of the diverse immune phenotype of SLE. On the basis of the SLE-related genes found in this study, we suggest that the interferon-related immune pathway is important in the pathogenesis of SLE. IFIT1 is the first gene described as a candidate gene for SLE, and may function by activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor. IFIT1 and the interferon-related pathway may provide potential targets for novel interventions in the treatment of SLE.
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Proteínas Portadoras/genética , Lupus Eritematoso Sistémico/genética , Proteínas Adaptadoras Transductoras de Señales , Adulto , Proteínas Portadoras/metabolismo , Femenino , Perfilación de la Expresión Génica/métodos , Predisposición Genética a la Enfermedad , Glutatión Transferasa/metabolismo , Humanos , Inmunofenotipificación , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Masculino , Familia de Multigenes , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa/métodos , Unión Proteica/genética , ARN Mensajero/genética , Proteínas de Unión al ARN , Proteínas Recombinantes de Fusión/metabolismo , Regulación hacia ArribaRESUMEN
Epidemiologic studies suggest a strong genetic component for susceptibility to systemic lupus erythematosus (SLE). To investigate the genetic mechanism of pathogenesis of SLE, we studied the difference in gene expression of peripheral blood cells between 10 SLE patients and 18 healthy controls using oligonucleotide microarray. When gene expression for patients was compared to the mean of normal controls, among the 3002 target genes, 61 genes were identified with greater than a two-fold change difference in expression level. Of these genes, 24 were upregulated and 37 downregulated in at least half of the patients. By the Welch's ANOVA/Welch's t-test, all these 61 genes were significantly different (P<0.05) between SLE patients and normal controls. Among these genes with differential expression, IFN-omega and Ly6E (TSA-1/Sca-2) may play an important role in the mechanism of SLE pathogenesis. TSA-1 antigens may represent an important alternative pathway for T-cell activation that may be involved in IFN-mediated immunomodulation. Hierarchical clustering showed that patient samples were clearly separated from controls based on their gene expression profile. These results demonstrate that high-density oligonucleotide microarray has the potential to explore the mechanism of pathogenesis of systemic lupus erythematosus.
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Perfilación de la Expresión Génica , Lupus Eritematoso Sistémico/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Adolescente , Adulto , Femenino , Humanos , Leucocitos/metabolismo , MasculinoRESUMEN
A prospective echocardiographic and clinical study was performed on 84 Chinese patients with systemic lupus erythematosus (SLE) and 99 controls to investigate the prevalence and the mechanism of pulmonary hypertension (PH) in SLE. Comparison between Doppler estimation and catheterization measurement was made in 12 cases to validate the predictive method. Compared to normal subjects, lupus patients had significantly increased systolic pulmonary artery pressure (SPAP) (29.59 +/- 12.52 vs 19.64 +/- 5.82, P < 0.001), mean pulmonary artery pressure (MPAP) (15.11 +/- 7.36 vs 10.21 +/- 4.72, P < 0.001) and total pulmonary resistance (TPR) (315.85 +/- 190.65 vs 220.37 +/- 55.92, P < 0.001). Nine of the 84 patients presented PH, defined as SPAP < 30 mmHg and MPAP > 20 mmHg. Pulmonary hypertensive patients had higher serum endothelin (ET) than non-pulmonary hypertensive patients, were more commonly in active stages, and presented Raynaud's phenomenon and rheumatoid factors. ET level was correlated with echocardiographic pulmonary pressure. Pulmonary hypertension commonly occurs in Chinese patients with SLE (11%), and it correlates with the lupus activity and the elevation of serum endothelin.
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Endotelinas/sangre , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Lupus Eritematoso Sistémico/complicaciones , Adolescente , Adulto , Anciano , Cateterismo Cardíaco , China/epidemiología , Ecocardiografía Doppler , Femenino , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/epidemiología , Modelos Lineales , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Valores de ReferenciaRESUMEN
Labial salivary gland biopsy (LSG-B) along with Schirmer test and kerato-conjunctival staining with fluorescein dye was performed in 196 patients with suspected Sjogren's syndrome (SS). Of the 196 patients, 117 were found to have 2 or more lymphocytic focus scores (LFS/4mm2) on their LSG-B specimens. 92 of them having keratoconjunctivitis sicca (KCS) as well met the diagnostic criteria of SS. Among the cases (25) without KCS, 16 with another CTD were diagnosed as secondary SS. 9 cases were classified as probable primary SS in this study because they had clinical manifestations of SS. Of the 11 cases with KCS only, 6 with another CTD were diagnosed as secondary SS; 5 befitted primary SS for abnormal findings on sialography. We also found that lymphocytic infiltration in LSG-B was much more severe in primary SS than in secondary SS; this could be attributed to the use of immunotherapy for the accompanying CTD in secondary SS. There was good association in our study between the severity of lymphocytic infiltration and systemic involvement.
Asunto(s)
Labio/patología , Glándulas Salivales/patología , Síndrome de Sjögren/patología , Adolescente , Adulto , Anciano , Biopsia , Femenino , Humanos , Queratoconjuntivitis Seca/complicaciones , Queratoconjuntivitis Seca/patología , Masculino , Persona de Mediana Edad , Síndrome de Sjögren/complicacionesRESUMEN
A method for detection of anticardiolipin (ACL) antibodies with enzyme-linked immunosorbent assay was developed. Microtitre plates were coated with cardiolipin at a concentration of 20 micrograms/ml by evaporation under 4 degree centigrade overnight. Non-specific binding of diluted sera was eliminated by blocking of plates with 10% fetal calf serum in phosphate buffered saline (FCS/PBS) for 2 hours at room temperature. Sera (50 microliters/well) at a dilution of 1:100 were incubated for 2 hours at room temperature. Horseradish peroxidase conjugated rabbit anti-human IgG, IgM, IgA at a dilution of 1:2000, 1:1000, 1:500 respectively was added to the wells, and incubated for one and half hours at room temperature. The results were read at 490nm after incubation with substrates at 37 degree centigrade. 85 patients with systemic lupus erythematosus (SLE), 45 with rheumatoid arthritis (RA), 25 with progressive systemic scleroderma (PSS), and 18 primary Sjogren's syndrome were tested. The frequency of ACL antibody in SLE (48%) was much higher than that in RA (11%), PSS (12), SS (5.5). Three isotypes of ACL (IgG, IgM, IgA) were detected in the study with predominance of IgG isotype. ACL antibody was significantly associated with thrombosis, cutaneous vasculopathy, thrombocytopenia, and spontaneous abortion in patients with SLE. Strong relationship between ACL antibody and lupus anticoagulant was found. There was no correlation between ACL and anti-DNA antibodies, nor was ACL and VDRL test. The level of ACL antibody could be reduced by use of corticosteroids.