RESUMO
OBJECTIVE: To explore genetic polymorphisms of the Wnt/ß-catenin signalling pathway in primary SS (PSS). METHODS: We included 98 patients with PSS and 165 healthy volunteers. Genomic DNA was extracted from peripheral blood samples. Through an open-array platform of low density, we genotyped 25 polymorphisms from 14 genes (WISP1, DKK1, SOST, FRZB, LRP1, LRP4, LRP5, LRP6, GSKB, ADAMTS5, GDF5, FMN2, ADIPOQ and COL11A1) involved in the Wnt/ß-catenin signalling pathway. We compared the allelic and genotypic frequencies with Fisher's exact test and logistic regression analysis adjusted by age, gender and individual admixture, as well as bootstrap-resampling analysis. We assessed the gene-gene interaction by the multifactor dimensionality reduction method. RESULTS: We found a positive significant association with four polymorphisms: LRP5 rs606989, FRZB rs409238, GSK3B rs2037547 and ADIPOQ rs2241766. All of them conferred risk for PSS, being the highest among subjects carrying three to four risk alleles (P < 0.001). According to a multifactor dimensionality reduction analysis, the best models included the LRP5 (rs606989), FRZB (rs409238) and ADIPOQ (rs2241766) polymorphisms. CONCLUSION: LRP5, FRZB and ADIPOQ genes related in the Wnt/ß-catenin signalling pathway increased the risk of PSS. Further research is needed to establish their functional role in this clinical entity.
Assuntos
Alelos , Frequência do Gene , Polimorfismo de Nucleotídeo Único , Síndrome de Sjogren/genética , Proteínas Wnt/genética , Via de Sinalização Wnt/genética , beta Catenina/genética , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION AND AIM: Association of vitamin D deficiency (VDD) with fatty liver (FL) disease is controversial. The purpose of this study was to analyze the association of VDD with FL. MATERIAL AND METHODS: Cross-sectional study. Data on cardiovascular risk factors, medications, alcohol intake, smoking, diet, and physical activity were obtained. Biochemical, anthropometric, and blood pressure variables were measured. The 25-hydroxyvitamin D (25(OH)D) was quantified through chemoluminescence. The presence of FL, defined as a liver/spleen attenuation index lower than 1.0, was identified through computed axial tomography (CAT). RESULTS: The study included 1,467 subjects (49.7% men) with a mean age of 53.3 ± 9.3 years and BMI of 28.3 ± 4.0 kg/m2. Only 11% had optimum values of vitamin D, and 25(OH)D concentration was lower in participants with FL. Multivariate logistic regression models, adjusted for age, gender, BMI, sampling season, glucose, total cholesterol, triglycerides, HOMA-IR, hs-CRP, ALT, AST, and elevated VAT, revealed an association between FL and vitamin D (VD) insufficiency (RM 1.61 [0.99-2.61]) and with VDD (RM 1.68 [1.02-2.77]); however, statistical significance was lost when including caloric consumption and physical activity in the model. CONCLUSIONS: In Mexican adults, deficient VD concentration and FL were not independently associated of caloric consumption and physical activity.
Assuntos
Fígado Gorduroso/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adulto , Biomarcadores/sangue , Estudos Transversais , Ingestão de Energia , Exercício Físico , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Tomografia Computadorizada por Raios X , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnósticoRESUMO
To compare the distribution of HLA-A, B, DRB1 and DQB1 alleles among Mexican patients with primary Sjögren Syndrome (pSS), secondary SS (sSS), connective tissue disease (CTD) without (w/o) SS and historical ethnically healthy controls. We included 28 pSS, 30 sSS, 96 CTD w/o SS patients and 234 controls. HLA-A, B, DRB1 and DQB1 were amplified and sequenced using the Allele SEQR Sequenced Based Typing Kits and analyzed on the ABI Prism*3130 DNA Analyzer using the Assign software. Gene frequencies were obtained by direct counting. Contingence tables of 2 × 2 were generated and analyzed by the Mantel-Haenzel χ (2) or Fisher's test (EPIINFO program). We reported odds ratios (OR) and corrected p values. SS patients showed increased frequencies of A*68:01 and DRB1*14:06 alleles when compared to CTD w/o SS (OR 4.43, 95 % CI 1.35-14.14, p = 0.007 and OR 14, 95 % CI 1.68-116, p = 0.001, respectively) and a higher prevalence of DRB1*01:01 (OR 5.9, 95 % CI 2.13-16.56, p = 0.003) and HLA-B*35:01 (OR 3.70, 95 % CI 1.92-7.12, p = 0.004) when compared with controls. pSS patients had a higher frequency of DRB1*14:06 allele than sSS (OR 16, 95 % CI 1.59-390, p = 0.001). Anti-Ro/SSA positivity was associated with B*51:01 (OR 10.11, 95 % CI 1.09-245, p = 0.02) and DRB1*03:01 alleles (OR 4.26, 95 % CI 1.01-18.89, p = 0.029), whereas the A*01:01 allele was associated with anti-La/SSB positivity (OR 4.75, 95 % CI 1.32-16.92, p = 0.003). In our population, the DRB1*14:06 allele was associated with primary and secondary SS implying that both varieties bear a similar immunogenetic background.
Assuntos
Antígenos HLA/genética , Síndrome de Sjogren/genética , Adulto , Idoso , Alelos , Feminino , Frequência do Gene , Humanos , Imunogenética , Masculino , México , Pessoa de Meia-Idade , Síndrome de Sjogren/imunologiaRESUMO
UNLABELLED: Oxygen is a neonatal health hazard that should be avoided in clinical practice. In this review, an international team of neonatologists and nurses assessed oxygen saturation (SpO2 ) targeting in preterm infants and evaluated the potential weaknesses of randomised clinical trials. CONCLUSION: SpO2 of 85-89% can increase mortality and 91-95% can cause hyperoxia and ill effects. Neither of these ranges can be recommended, and wider intermediate targets, such as 87-94% or 88-94%, may be safer.
Assuntos
Hiperóxia/prevenção & controle , Hipóxia/prevenção & controle , Recém-Nascido Prematuro/sangue , Terapia Intensiva Neonatal/normas , Oxigênio/sangue , Humanos , Recém-Nascido , Monitorização Fisiológica , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Aim: To analyze the association of NKX2.5 gene with congenital heart disease (CHD), and to determine if the variants rs703752, rs3729753 and rs2277923 increase the risk for developing CHD. Materials & methods: PubMed, EBSCO and Web of Science databases were screened to identify eligible studies. Through a comprehensive meta-analysis software, the association between NKX2.5 gene variants and susceptibility of CHD was calculated by pooled odd ratio (ORs) and 95% CI. Results: We observed that the allelic model of rs703752 and rs2277923 increased the risk in the overall population: OR = 1.24; 95% CI: 1.00-1.55; Z p-value = 0.049; OR = 1.18; 95% CI: 0.01-1.37; Z p-value = 0.036; respectively. Conclusion: Our results suggested that the rs703752 and rs2277923 polymorphisms of the NKX2.5 gene are associated with CHD.
Assuntos
Cardiopatias Congênitas/genética , Proteína Homeobox Nkx-2.5/genética , Proteína Homeobox Nkx-2.5/metabolismo , Alelos , Bases de Dados Genéticas , Frequência do Gene , Predisposição Genética para Doença , Cardiopatias Congênitas/metabolismo , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Trypanosoma cruzi antigens TSA-1 and Tc24 have shown promise as vaccine candidates in animal studies. We evaluated here the recall immune response these antigens induce in Chagasic patients, as a first step to test their immunogenicity in humans. We evaluated the in vitro cellular immune response after stimulation with recombinant TSA-1 (rTSA-1) or recombinant Tc24 (rTc24) in mononuclear cells of asymptomatic Chagasic chronic patients (n = 20) compared to healthy volunteers (n = 19) from Yucatan, Mexico. Proliferation assays, intracellular cytokine staining, cytometric bead arrays, and memory T cell immunophenotyping were performed by flow cytometry. Peripheral blood mononuclear cells (PBMC) from Chagasic patients showed significant proliferation after stimulation with rTc24 and presented a phenotype of T effector memory cells (CD45RA-CCR7-). These cells also produced IFN-γ and, to a lesser extent IL10, after stimulation with rTSA-1 and rTc24 proteins. Overall, both antigens recalled a broad immune response in some Chagasic patients, confirming that their immune system had been primed against these antigens during natural infection. Analysis of HLA-A and HLA-B allele diversity by PCR-sequencing indicated that HLA-A03 and HLA-B07 were the most frequent supertypes in this Mexican population. Also, there was a significant difference in the frequency of HLA-A01 and HLA-A02 supertypes between Chagasic patients and controls, while the other alleles were evenly distributed. Some aspects of the immune response, such as antigen-induced IFN-γ production by CD4+ and CD8+ T cells and CD8+ proliferation, showed significant association with specific HLA-A supertypes, depending on the antigen considered. In conclusion, our results confirm the ability of both TSA-1 and Tc24 recombinant proteins to recall an immune response induced by the native antigens during natural infection in at least some patients. Our data support the further development of these antigens as therapeutic vaccine against Chagas disease.
Assuntos
Antígenos de Protozoários/imunologia , Doença de Chagas/imunologia , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Imunidade Celular , Memória Imunológica , Trypanosoma cruzi/imunologia , Adulto , Idoso , Proliferação de Células , Citocinas/análise , Feminino , Citometria de Fluxo , Frequência do Gene , Variação Genética , Genótipo , Humanos , Imunofenotipagem , Leucócitos Mononucleares/imunologia , Masculino , México , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
INTRODUCTION: Suicide is known as a major health concern worldwide. There is evidence for the role of brain-derived neurotrophic factor (BDNF) in suicide behavior. Therefore, this factor has been proposed as a biomarker for suicide behavior. Clinical studies have measured BDNF concentrations at central and peripheral levels. As a consequence, the aim of this study was to assess BDNF levels in blood plasma and serum to see whether there is a difference in concentrations in patients with suicide behavior when compared to those in controls, using a meta-analysis approach. METHODS: We conducted a systematic review and meta-analysis. The search strategy was performed using three databases: PubMed, EBSCO and ScienceDirect. The meta-analysis included a total of nine case-control studies, six measured the BDNF level in serum and three in plasma in suicide behavior. RESULTS: A decrease in BDNF levels in plasma was observed (d = -0.73, 95% CI -1.42 to -0.03 pg/ml). In the case of serum concentrations, no BDNF differences were encountered between cases and controls (d = 0.09, 95% CI -0.31 to 0.13 ng/ml, p(Q) = .92). CONCLUSIONS: According to the results found in the present meta-analysis, the plasma BDNF level could be suggest as a potential biomarker in suicide behavior. However, since the number of studies included in the analysis is limited, a larger number is necessary to determine conclusively the role of BDNF as a biomarker in suicide behavior.
Assuntos
Sintomas Comportamentais/sangue , Fator Neurotrófico Derivado do Encéfalo , Suicídio , Biomarcadores/análise , Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/análise , Fator Neurotrófico Derivado do Encéfalo/sangue , HumanosRESUMO
The polymorphisms of the serotonin receptor 2C (HTR2C) gene have been proposed to influence suicidal behavior. The aim of our study was to explore the role of the HTR2C gene variant Cys23Ser (rs6318) in the pathogenesis of suicidal behavior through a systematic review and meta-analysis. The search was performed using EBSCO and PubMed databases. To be included in the analysis, the studies had to evaluate suicidal behavior (attempted, ideation, or completed suicide). The results of the meta-analysis were expressed as odds ratios (ORs). Because HTR2C lies on chromosome X, pooled ORs were calculated, respectively, for each of the models used, namely: allelic, homozygous, dominant, and recessive for the female group and allelic for the male group. The meta-analysis comprised 3867 individuals, including 1668 cases and 2199 controls. The HTR2C Cys23Ser (rs6318) polymorphism did not show a significant association with suicidal behavior either in women (OR: 0.75; 95% confidence interval: 0.55-1.00) or in men (OR: 0.89; 95% confidence interval: 0.64-1.23). Similarly, nonsignificant associations were observed for all of the genetic models used in any of the populations/subgroups studied. Our findings suggest that the rs6318 (Cys23Ser) polymorphism is not associated with suicidal behavior. However, because of the study limitations, we suggest more researches should be performed, increasing the sample sizes and statistical power, to determine the association between the rs6318 variant and suicidal behavior.
Assuntos
Receptor 5-HT2C de Serotonina/genética , Comportamento Autodestrutivo/genética , Suicídio/psicologia , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Receptor 5-HT2C de Serotonina/metabolismo , Fatores de Risco , Ideação Suicida , Tentativa de Suicídio/psicologiaRESUMO
The anti-atherogenic properties of high-density lipoproteins (HDLs) may be related to their structure and metabolism. The HDL physicochemical characteristics that determine their plasma clearance during treatment with statins and fibrates are not well understood. In this study, we analyzed HDL-apo AI fractional catabolic rates (FCRs), size distributions, and the lipid composition of the HDL subclasses in New Zealand white rabbits with exogenous dyslipidemia that received low doses of atorvastatin and fenofibrate. Hypercholesterolemia decreased only partially with the combination of both drugs. HDL size distribution shifted toward larger particles among the groups of rabbits that received atorvastatin, fenofibrate, or their combination, compared with both the control group and the dyslipidemic group. The HDL subclasses were significantly rich in cholesterol in each of the groups compared with controls. The structural changes noted in the HDL subclasses were not associated with impaired plasma paraoxonase-1 (PON1) activity. The groups receiving monotherapy and the drug combination group were all associated with a higher apo AI FCR value compared with both the dyslipidemic rabbits and the control group. In conclusion, the combination of atorvastatin and fenofibrate induced a more favorable HDL subclass profile than did the individual use of these drugs. Similarly, the apo AI FCR values were augmented in every group receiving drug treatment (either monotherapy or combination therapy) in the setting of hypercholesterolemia. The anti-atherogenic properties of HDLs, excluding their capacity to bind PON1, may be enhanced by the structural and metabolic modifications induced by the combination of atorvastatin and fenofibrate.
Assuntos
Apolipoproteína A-I/sangue , Atorvastatina/farmacologia , HDL-Colesterol/sangue , Fenofibrato/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/farmacologia , Animais , Arildialquilfosfatase/metabolismo , Atorvastatina/uso terapêutico , Glicemia/metabolismo , Sinergismo Farmacológico , Fenofibrato/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipolipemiantes/uso terapêutico , Cinética , Lipídeos/sangue , Masculino , CoelhosRESUMO
Tumor necrosis factor alpha (TNF-alpha) gene is located within the class III region of the major histocompatibility complex (MHC) on the short arm of the human sixth chromosome. Two polymorphisms in the promoter region of the TNF-alpha gene (-308 and -238) have been associated with the genetic susceptibility to develop ulcerative colitis in both Caucasian and Asian populations. The aim of this study was to determine the role of TNF-alpha gene polymorphisms and those from the HLA-DRB1 locus in the susceptibility to develop ulcerative colitis (UC). Eighty Mexican mestizo patients suffering from UC and 99 ethnically matched unrelated healthy controls were genotyped for two TNF-alpha polymorphisms located in the promoter region (positions -308, -238) by polymerase chain reaction (PCR) and amplification refractory mutation system (ARMS) as well as high resolution DNA typing for HLA-DRB1 alleles were performed. The frequency of individuals positive for allele 2 of the TNF(-308) polymorphism was significantly higher in UC patients than healthy controls (23.7% versus 3%, pC = 0.00002; OR = 10.1; CI 95% = 2.69-26.8). No statistically significant deviation from normality was found between TNF*A (-238) and UC Mexican patients. Clinical manifestations such as pancolitis, extraintestinal manifestations and colectomy were not associated with any of the TNF promoter region polymorphisms. However, HLA-DRB1*15 was found to be associated with pancolitis and HLA-DRB1*0103 with the need of proctocolectomy. In conclusion, this clinical differential pattern of association distinguished in two neighboring loci within the MHC region suggest an independent role of the TNF locus in the genetic susceptibility to develop UC.