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1.
Hum Immunol ; 75(8): 808-15, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24929142

ABSTRACT

BACKGROUND: Gastric cancer (GC) is a progressive process initiated by Helicobacter pylori-induced inflammation. Initial recognition of H. pylori involves Toll-like receptors (TLRs), central molecules in the host inflammatory response. Here, we investigated the association between novel polymorphisms in genes involved in the TLR signalling pathway, including TLR2, TLR4, LBP, MD-2, CD14 and TIRAP, and risk of H. pylori infection and related GC. METHODS: A case-control study comprising 310 ethnic Chinese individuals (87 non-cardia GC cases and 223 controls with functional dyspepsia) was conducted. Twenty-five polymorphisms were detected by MALDI-TOF mass spectrometry, PCR, PCR-RFLP and real-time PCR. RESULTS: Seven polymorphisms showed significant associations with GC (TLR4 rs11536889, TLR4 rs10759931, TLR4 rs1927911, TLR4 rs10116253, TLR4 rs10759932, TLR4 rs2149356 and CD14 -260 C/T). In multivariate analyses, TLR4 rs11536889 remained a risk factor for GC (OR: 3.58, 95% CI: 1.20-10.65). TLR4 rs10759932 decreased the risk of H. pylori infection (OR: 0.59, 95% CI: 0.41-0.86). Statistical analyses assessing the joint effect of H. pylori infection and the selected polymorphisms revealed strong associations with GC (TLR2, TLR4, MD-2, LBP and TIRAP polymorphisms). CONCLUSIONS: Novel polymorphisms in TLR2, TLR4, MD-2, LBP, CD14 and TIRAP, genes encoding important molecules of the TLR signalling pathway, showed clear associations with H. pylori-related GC in Chinese.


Subject(s)
Genetic Predisposition to Disease , Helicobacter Infections/genetics , Stomach Neoplasms/genetics , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/genetics , Acute-Phase Proteins/genetics , Acute-Phase Proteins/immunology , Aged , Carrier Proteins/genetics , Carrier Proteins/immunology , Case-Control Studies , China , Female , Gene Expression , Helicobacter Infections/complications , Helicobacter Infections/immunology , Helicobacter Infections/microbiology , Helicobacter pylori/physiology , Humans , Lipopolysaccharide Receptors/genetics , Lipopolysaccharide Receptors/immunology , Lymphocyte Antigen 96/genetics , Lymphocyte Antigen 96/immunology , Male , Membrane Glycoproteins/genetics , Membrane Glycoproteins/immunology , Middle Aged , Polymorphism, Genetic , Receptors, Interleukin-1/genetics , Receptors, Interleukin-1/immunology , Signal Transduction , Stomach Neoplasms/complications , Stomach Neoplasms/immunology , Stomach Neoplasms/microbiology , Toll-Like Receptor 2/immunology , Toll-Like Receptor 4/immunology
2.
Rev. colomb. reumatol ; 16(2): 132-137, jun. 2009. ilus, tab
Article in Spanish | LILACS | ID: lil-636801

ABSTRACT

La enfermedad de Kawasaki es una vasculitis sistémica, cuya principal complicación es la afectación de las arterias coronarias. El propósito de este estudio retrospectivo fue el de evaluar en 48 pacientes colombianos la tasa y los factores asociados a la afección cardiaca. El tiempo promedio desde el primer síntoma hasta el diagnóstico fue de 10,5 días. Las alteraciones cardiacas fueron registradas en 13 (27%) pacientes: 10 con afección coronaria y 3 con otro tipo de manifestaciones cardiacas. Cuarenta y un pacientes (85,4%) recibieron inmunoglobulina. La edad del paciente (OR: 0,91, IC 95%: 0,85-0,98, p = 0,01) y el tiempo trascurrido hasta el diagnóstico (OR: 1,21, IC 95%: 1,05-1,41, p = 0,01) fueron factores respectivamente influyentes en alteraciones cardiacas y coronarias. La alta tasa de manifestaciones cardiacas es similar a la reportada en otras poblaciones latinoamericanas.


Kawasaki disease (KD) is a systemic vasculitis, whose main complication is the coronary arteries involvement. This was a retrospective study in which 48 Colombian KD patients were included, and the rate and associated factors to cardiac involvement were investigated. The mean time from the first symptom until the diagnosis was 10.5 days. Cardiac involvement was registered in 13 (27%) patients, of whom 10 presented with coronary disease and 3 with a different cardiac manifestations. Forty-one patients (85.4%) received IV immunoglobulin. By multivariate analysis, the patient's age (OR: 0.91, 95% CI: 0.85-0.98, p = 0.01) and the lapse of time between onset of symptoms and diagnosis (OR: 1.21, 95% CI: 1.05-1.41, p = 0.01) were associated factors influencing cardiac involvement and coronary disease, respectively. The high rate of cardiac compromise in Colombian patients agrees with that observed in other Latin American populations.


Subject(s)
Humans , Male , Female , Incidence , Cardiovascular Nursing , Colombia , Coronary Disease , Mucocutaneous Lymph Node Syndrome
3.
Clin Rheumatol ; 28(7): 767-75, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19277815

ABSTRACT

The objective of this study was to examine the clinical and genetic variables associated with extra-articular rheumatoid arthritis (ExRA). This was a cross-sectional study in which 538 Northwestern Colombian patients with rheumatoid arthritis (RA) were included. Information about demographics and clinical characteristics including disease activity, inflammatory markers, co-morbidities, cardiovascular (CV) risk factors, history of familial autoimmunity and therapy was recorded. The presence of HLA "shared epitope" (SE) alleles and TNF gene polymorphism was assessed. A multivariate statistical analysis was performed. ExRA was found in 32% of the patients, of which nodulosis, Sjögren's syndrome, and lung involvement were registered in 21%, 9%, and 4% of patients, respectively. Patients with ExRA were older than patients without it and they presented longer disease duration as well. Thus, an association between disease duration and ExRA manifestations was also observed. Patients with ExRA presented significant higher titers of anti-CCP antibodies as compared to patients without ExRA. Hypertension and thrombosis were significantly associated with ExRA. Never having smoked constituted a protective factor against ExRA onset. Associations between ExRA and the presence of traditional CV risk factors were also found. Our results show that duration of RA, CV disease and high titers of anti-CCP antibodies are associated with ExRA in Colombian patients with RA, and highlight the importance of preventing smoking in those who are prone to develop autoimmune diseases including RA.


Subject(s)
Arthritis, Rheumatoid/complications , Cardiovascular Diseases/etiology , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Autoantibodies/blood , Cardiovascular Diseases/genetics , Cardiovascular Diseases/immunology , Colombia/epidemiology , Cross-Sectional Studies , Female , Genotype , HLA-DQ Antigens/genetics , HLA-DQ beta-Chains , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Histocompatibility Testing , Humans , Indians, South American , Male , Middle Aged , Peptides, Cyclic/immunology , Risk Factors , Time Factors , White People
4.
Clin Rheumatol ; 28(7): 757-65, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19277816

ABSTRACT

The objective of this study was to analyze epidemiological tendencies of systemic sclerosis (SSc) around the world in order to identify possible local variations in the presentation and occurrence of the disease. A systematic review of the literature was performed through electronic databases using the keywords "Systemic Sclerosis" and "Clinical Characteristics." Out of a total of 167 articles, 41 were included in the analysis. Significant differences in the mean age at the time of diagnosis, subsets of SSc, clinical characteristics, and presence of antibodies were found between different regions of the word. Because variations in both additive and nonadditive genetic factors and the environmental variance are specific to the investigated population, ethnicity and geography are important characteristics to be considered in the study of SSc and other autoimmune diseases.


Subject(s)
Autoimmunity/physiology , Global Health , Scleroderma, Systemic , Adult , Age Factors , Animals , Disease Models, Animal , Environment , Ethnicity , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/epidemiology , Scleroderma, Systemic/etiology , Sex Factors
5.
Autoimmun Rev ; 8(4): 325-31, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19041429

ABSTRACT

BACKGROUND: Autoimmune hepatitis (AIH) is a chronic liver disease to which different Human Leukocyte Antigens (HLA) have been associated, according to the ethnic/geographical group affected, age of presentation, prognosis, and serologic profile. OBJECTIVE: To identify common HLA class II alleles contributing to susceptibility to AIH in Latin American population. METHODS: The present study was held through a systematic review of the literature, followed by a meta-analysis of 694 cases and 1769 controls of all case-control studies that supplied enough information for odd ratio and 95% confidence interval calculation conducted to date in Latin America. RESULTS: The serological group DQ2 was found to be risk factor for AIH, while DR5 and DQ3 were found to be protective factors in this population. At the allelic level, DQB1*02, DQB1*0603, DRB1*0405, and DRB1*1301, were found to be risk factors, while DRB1*1302 and DQB1*0301 alleles were protective factors. The physicochemical similarities and differences of critical amino acids encoding the peptide binding groove at pockets P1, P4, and P6 of these HLA molecules, elucidates their influence in the development of disease. CONCLUSION: The current study strengthens the HLA component of AIH in Latin America and its relationship to other populations around the world.


Subject(s)
Genetic Predisposition to Disease , Hepatitis, Autoimmune/genetics , Histocompatibility Antigens Class II/genetics , Histocompatibility Testing , Adult , Case-Control Studies , Child , Child, Preschool , Female , Hepatitis, Autoimmune/epidemiology , Histocompatibility Antigens Class II/classification , Histocompatibility Antigens Class II/metabolism , Humans , Latin America/epidemiology , Male , Young Adult
6.
Semin Arthritis Rheum ; 38(2): 71-82, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18395773

ABSTRACT

OBJECTIVES: Rheumatoid arthritis (RA) is associated with an increased prevalence of cardiovascular disease (CVD). Since atherosclerosis development is a gradual process of damage inside the artery wall, and the phenotype-genotype correlation of complex diseases may vary depending on ethnicity, we sought to investigate the influence of clinical features, routine inflammatory markers, and the genetic component of RA on different stages of atherosclerosis in northwestern Colombian patients with RA. METHODS: A group of 140 patients with RA were enrolled in this study. All patients underwent a noninvasive evaluation of endothelial function by flow-mediated vasodilation (FMV) and an assessment of carotid intima-media thickness (IMT) by high-resolution B-mode ultrasonography. The patients were classified into 3 categories: endothelial dysfunction (FMV <5%), increased IMT (0.91-1.29 mm), and plaque (IMT >1.30 mm). The risk of being in each category was assessed by investigating traditional and nontraditional cardiovascular risk factors. For each stage of atherosclerosis development, we searched for nontraditional risk factors that were significantly associated with the stage after adjusting for traditional risk factors and current age. RESULTS: Rheumatoid factor seropositivity was significantly associated with endothelial dysfunction (adjusted odds ratio, AOR = 3.0). A duration of RA >10 years (AOR = 29.0) and being a carrier of an HLA-DRB1 shared epitope allele (AOR = 4.8) were associated with atherosclerotic plaque. No association of extra-articular manifestations, anticyclic citrullinated peptide (anti-CCP3) antibodies, and tumor necrosis factor -308 polymorphism with CVD was found. CONCLUSIONS: Our results reveal the presence of RA-related risk factors for CVD which act independently of traditional risk factors. These factors can be used by clinicians to predict CVD in RA patients, and this data should assist in the development of public health policies in our population for the improvement of patient outcomes.


Subject(s)
Arthritis, Rheumatoid/complications , Carotid Artery Diseases/pathology , Endothelium, Vascular/physiopathology , Adult , Arthritis, Rheumatoid/blood , Carotid Artery Diseases/blood , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/etiology , Colombia , Endothelium, Vascular/diagnostic imaging , Female , Humans , Male , Middle Aged , Rheumatoid Factor/blood , Risk Assessment , Risk Factors , Severity of Illness Index , Tunica Intima/diagnostic imaging , Tunica Intima/pathology , Tunica Media/diagnostic imaging , Tunica Media/pathology , Ultrasonography
7.
J Rheumatol ; 35(2): 244-50, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18203318

ABSTRACT

OBJECTIVE: Considering the significant morbidity and mortality of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc) and the lack of precise information on disease in Latin America, we investigated the clinical and laboratory characteristics associated with PAH in Colombian patients with SSc and review the literature. METHODS: This multicenter study included patients followed at 5 rheumatology units that were systematically assessed using a pretested questionnaire on clinical and immunological variables, focusing on PAH. Conditional logistic regression was employed to assess association between PAH and specific clinical characteristics. A systematic review of the literature was performed through electronic databases. RESULTS: Of a total of 349 patients with SSc, 61 (17%) met the criteria for PAH. Pulmonary fibrosis [adjusted odds ratio (AOR) 7.37, 95% CI 3.67-14.81, p < 0.0001], microstomia (AOR 3.3, 95% CI 1.70-6.28, p < 0.0001), gastroesophageal reflux (AOR 2.41, 95% CI 1.31-4.43, p = 0.005), dysphagia (AOR 2.7, 95% CI 1.49-4.77, p = 0.001), hyperpigmentation (AOR 2.15, 95% CI 1.11-4.16, p = 0.02), and hypopigmentation (AOR 2.4, 95% CI 1.26-4.64, p = 0.008) were the most prevalent clinical characteristics associated with PAH, while anemia (AOR 5.4, 95% CI 1.98-14.93, p = 0.001) was observed as the unique laboratory risk factor. Association between subtypes of SSc and PAH was not observed. Significant differences in both clinical and laboratory data were observed among different series. CONCLUSION: PAH may be a frequent complication of SSc in the Colombian population regardless of disease subtype. The identified clinical and laboratory risk factors might assist earlier diagnosis and guide decisions on therapeutic interventions on this critical complication of SSc. The reasons underlying the reported divergences among patients from different ethnicities are not fully understood, but it is most likely that both genetic and environmental factors are responsible for them.


Subject(s)
Hypertension, Pulmonary/complications , Scleroderma, Systemic/complications , Adult , Aged , Colombia/epidemiology , Female , Gastroesophageal Reflux/complications , Humans , Hypertension, Pulmonary/epidemiology , Male , Middle Aged , Odds Ratio , Pulmonary Fibrosis/complications , Risk Factors , Scleroderma, Systemic/epidemiology
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