ABSTRACT
Background: Cytotoxic T lymphocyte antigen-4 (CTLA-4) molecule is an important regulator of T cell activation involved in the down-regulation of immune response. Their polymorphisms +49 A/G and CT60 have been suggested to confer susceptibility to autoimmune endocrine disorders. The aim of this study was to determine the association of CTLA-4 gene polymorphisms with T1D in the Chilean population. We also wanted to study if the combined haplotypes of +49 A/G and CT60 had an impact on risk for T1D. Methods: To evaluate the impact of allelic variants CT60 and +49 A/G SNPs were studied in a Chilean population, including 248 T1D patients and 160 controls. Genotypes of both polymorphisms of CTLA-4 gene were determinate by PCR-restriction fragment polymorphism (PCRRFLP).Results: No statistical differences were observed when comparing patients with diabetes and controls for both CTLA-4 genotypes. However, the haplotype analysis between CT60 and +49 A/G showed an interesting combination of risk conformed by G*G combination with an OR of 1.648 [1.19- 2.28], (p = 0.002). Conclusions: The G*G haplotype could be a risk marker in patients with T1D in Chilean population.
Subject(s)
Humans , /genetics , Diabetes Mellitus, Type 1/genetics , Polymorphism, Genetic , Autoimmunity , Case-Control Studies , Chile , Diabetes Mellitus, Type 1/immunology , HaplotypesABSTRACT
Background: Pollution and viral infections could be associated with the incidence of type 1 diabetes mellitus. Aim: To look for associations between the temporal patterns of Type 1 Diabetes Mellitus (T1D) in infants younger than the age of 15years, and environmental factors, such as air pollution and viruses. Material and Methods: Data registries from hospitals, emergency services, and the Infantile Diabetes Foundation were reviewed, corresponding to children aged less than 15years, who received their first insulin injection between 2000 and 2007. The incidence of type 1 diabetes was computed for each epidemiological week. Environmental ozone and particulate matter rates for each week were obtained from Environmental services. Rates of influenza and respiratory syncytial virus infections were obtained from the epidemiological department of the Ministry of Health. An ecological Bayesian Poisson regression model was fitted, introducing the covariates, lagged covariates and errors, to estimate the incidence by epidemiological week. Results: Three factors were significant by the proposed model: particulate matter PPM 2.5 (relative risk (RR): 1.003) lagged by two weeks, influenza (RR: 0.1808) and RSV (RR: 1.021). Trends and seasonality were clearly controlled by these covariates, considering the epidemiological week as a counting period. Conclusions: These results show that environmental factors could be related to peaks of type 1 diabetes incidence.
Subject(s)
Adolescent , Humans , Infant , Air Pollutants/toxicity , Air Pollution/adverse effects , Diabetes Mellitus, Type 1/epidemiology , Influenza, Human/epidemiology , Ozone/adverse effects , Respiratory Syncytial Virus Infections/epidemiology , Chile/epidemiology , Diabetes Mellitus, Type 1/etiology , Incidence , Influenza, Human/complications , Particulate Matter/adverse effects , Poisson Distribution , Respiratory Syncytial Virus Infections/complicationsABSTRACT
Background: The programmed cell death 1 (PDCD-1) immune-receptor is a key element in the negative regulation of peripheral tolerance in T cells. The gene has several polymorphisms and can be associated with susceptibility to autoimmune diseases. Aim: To analyze the frequency and distribution of PD-1.3 polymorphism of PDCD-1 gene and explore its possible contribution as a susceptibility gene for type 1 diabetes (T1D). Patients and Methods: We analyzed 248 cases with T1D with recent diagnosis and 160 control children under 15 years of Santiago. Genetic polymorphism in PD-1 gene variant for PD-1.3 (rs 11568821) was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Comparison of genotype, allele frequency and consistency with respect to Hardy-Weinberg were analyzed using X2 tests and Fisher exact test. Results: There was a very low frequency of the genotype A/A, both in T1D patients and in controls (< 2 percent). The A/G genotype was more common in diabetic patients than in controls (41.6 and 18.8 percent respectively, p < 0.04). G/G genotype was more common in controls than in patients (79.4 and 56.8 percent respectively, p < 0.02). T1D patients carrying genotype G/G had a higher frequency of anti-GAD65 and anti-A-2 antibodies (81 and 67 percent respectively). Conclusions: The distribution of PD-1.3 genotype frequencies are similar to that reported elsewhere. Possibly, this genetic variant (rs 11568821) does not have an important marker role in Chilean T1D patients.
Subject(s)
Humans , Adolescent , Child , Diabetes Mellitus, Type 1/genetics , Polymorphism, Genetic , Programmed Cell Death 1 Receptor/genetics , Autoimmunity , Antibodies/analysis , Diabetes Mellitus, Type 1/immunology , Gene Frequency , Genetic Markers , GenotypeABSTRACT
Type 1 diabetes (T1D) results from autoimmune-mediated destruction of the pancreatic beta cells, a process that is conditioned by multiple genes and environmental factors. The process that destroys the pancreatic b cells in T1D is mediated by T cells and leads to a complex phenotype influenced by multiple factors. It has been more than 30 years since the publication of the first evidence suggesting the involvement of a specific chromosomal region, HLA, in modulating the risk for T1D. HLA locus has been known for decades to contribute strongly with the attributable to genetic risk. In addition to HLA, many proposed candidate loci have been described that are associated with risk of developing the disease, including the insulin gene (INS), PTPN22,CTLA-4, PD-1, IL2-RA and IFIH1 which together do not contribute more than 15 percent of the risk. This review compiled the data on T1D genes and discusses the major genetic impact of these genetic aspects in T1D etiology.
Subject(s)
Humans , Diabetes Mellitus, Type 1/genetics , Genetic Markers , DEAD-box RNA Helicases/genetics , /genetics , HLA Antigens/genetics , Genetic Predisposition to Disease , Insulin/genetics , /genetics , /geneticsABSTRACT
Background: Several polymorphisms of the CTLA4 gene have been associated with autoimmune diseases. The activation of induced cell death is the major event and caspase 3 represents the main protein for the apoptotic machinery, especially in lymphocytes. Aim: To correlate CTLA4 polymorphisms with caspase 3 expression in peripheral blood mononuclear cells (PBMC) simulating in vitro the glucose effect. Material and Methods: CTLA4 polymorphisms were determined by restriction fragment length polymorphisms (RFLPs). PBMC from 21 patients with type 1 diabetes aged 8.5 ± 4.3 years and 21 healthy subjects aged 18.3 ± 1.8 years, were stimulated under normal (5 mM) and toxic (14 mM) glucose conditions to assess its effect on the expression and activity of caspase 3. Relative abundance of caspase 3 mRNA was measured by semi quantitative RT-PCR and its activity, by a colorimetric assay. Results: When stimulated with 14mM glucose, PBMC of G allele carriers with type 1 diabetes had significantly lower relative mRNA abundance of caspase 3 (median value = 0.12, range 0.01-0.70 AU) compared with non-carriers (median value = 0.81, range 0.06-1.09 AU). When the incubation was carried out with the lower glucose concentration, a similar profile of caspase 3 activity was observed in diabetic patients carrying G allele (median value = 0.57, range 0.13-1.20 AU) as compared with non-carriers (median value = 0.89, range 0.14-5.50 AU). No significant changes after stimulating with glucose, were observed in PBMCs of the control group. Conclusions: PBMC of recently diagnosed patients with T1D, carrying the G allele in + 49A/G polymorphisms of CTLA4, have a decreased expression and activity of caspase 3.
Subject(s)
Adolescent , Child , Female , Humans , Male , /genetics , /deficiency , Diabetes Mellitus, Type 1/enzymology , Diabetes Mellitus, Type 1/genetics , Polymorphism, Genetic/genetics , Alleles , Apoptosis , Case-Control Studies , Genotype , Leukocytes, Mononuclear/enzymology , Polymorphism, Restriction Fragment LengthABSTRACT
Background: "Strong Families" is a family program aimed at preventing risk behaviors in adolescents from 10 to 14 years of age. It has been developed by the Pan American Health Organization (PAHO/WHO) and is based on the Iowa Strengthening Families Program. This program has been certified and has been proven to effectively prevent adolescent drug and alcohol abuse in several countries around the globe. Aim: To evaluate the Strong Families Program toward adjusting current parenting styles, aiming to decrease risk behaviors in Chilean adolescents. Material and Methods: A quasi-experimental study involving 120 families, selected from 6 schools within the Metropolitan Region of Santiago, Chile. A group of 129 adolescents and 124 parents were chosen by convenience to be intervened. A control group of 223 adolescents and 165 parents were not intervened. The families that underwent intervention attended to 7 educational sessions. The intervened and control groups were evaluated before intervention as well as 6 months after intervention, by means of self-administered evaluation tools. Results: The intervened parents showed significant parenting changes six months after intervention, which resulted in less yelling (p = 0.007), insults (p = 0.002) and lack of control when their children misbehaved (p = 0.008). Regarding the risk behaviors in the intervened and control adolescents, no changes were observed in terms of the consumption rate of tobacco, alcohol or illegal drug use, or in sexual risk behaviors. Conclusions: After six months of intervention, the Program proved to be effective in modifying parenting styles. However, no changes were observed in risk behaviors among adolescents, which could occur within a longer period of time, as reported in other studies.
Subject(s)
Adolescent , Child , Female , Humans , Male , Adolescent Behavior , Family Health/standards , Program Evaluation , Chile , Parent-Child Relations , Risk , Risk-TakingABSTRACT
Background: Hemolytic-uremic syndrome (HUS) is characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. Aim: To describe the characteñstics ofpatients with the diagnosis ofHUS in Chile, and to identify the most reliable early predictors oímorbidity and moñality. Material and methods: The clinical records ofpatients with HUS aged less than 15 years, attended between January 1990 and December 2003 in 15 hospitals, were reviewed. Demographic, clinical, biochemical, hematological parameters, morbidity and mortality were analyzed. Results: A cohort of 587 patients aged 2 to 8 years, 48 percent males, was analyzed. Ninety two percent had diarrhea. At the moment of diagnosis, anuria was observed in 39 percent of the patients, hypertension in 45 percent and seizures in 17 percent. Forty two percent required renal replacement therapy (RRT) and perítoneal dialysis was used in the majoríty of cases (78 percent). The most frequently isolated etiological agentwas Escherichia coli. Mortality rate was 2.9 percent in the acute phase of the disease and there was a positive correlation between mortality and anuria, seizures, white blood cell count (WCC) >20.000/mm³ and requirements of renal replacement therapy (p <0.05). Twelve percent of patients evolved to chronic renal failure and the risk factors during the acute phase were the need for renal replacement therapy, anuria, WCC >20.000/mm³, seizures and hypertension. Conclusions: The present study emphasizes important clinical and epidemiological aspeets ofHUSin a Chilean pediatricpopulation.
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Acute Kidney Injury , Anuria/etiology , Hemolytic-Uremic Syndrome/complications , Acute Kidney Injury , Anuria/epidemiology , Anuria/therapy , Child Health Services/statistics & numerical data , Chile/epidemiology , Follow-Up Studies , Hemolytic-Uremic Syndrome/mortality , Hemolytic-Uremic Syndrome/therapy , Hospitalization , Logistic Models , Prognosis , Renal Dialysis , Retrospective Studies , Risk FactorsABSTRACT
El carcinoma bronquioloalveolar (CABA) se presenta inicialmente en etapa de nódulo periférico, asistomático y estable por algunos años. En esta etapa el tratamiento tiene una sobrevida de 75 a 80 por ciento a cinco años. En los países desarrollados su diagnóstico se logra en esta estapa hasta en un 50 por ciento de los pacientes. La fase de microdiseminación canalicular corresponde a un estadio difuso del mal pronóstico. Nuestro propósito fue evaluar el diagnóstico precoz del CABA en el Instituto Nacional del Tórax (INT). Se realizó una revisión retrospectiva de estos pacientes usando la base de datos de cáncer pulmonar del INT durante 1994-1997. Se encontró 673 pacientes con cáncer pulmonar, de los cuales 15 (2,2 por ciento) eran del subtipo CABA confirmado por citología y/o histología. El promedio de edad de estos pacientes fue 64 años. La relación maculino/femenino = 1,1 y 56,2 por ciento eran fumadores. En etapa de nódulo ingresaron dos pacientes con CABA (13,3 por ciento) que fueron tratados con lobectomía, sobreviviendo 56 y 30 meses respectivamente. El promedio de sobrevida de los 13 pacientes con tratamiento paliativo fue 9 meses. En este estudio los pacientes con CABA en cuanto a promedio de edad, distribución por sexo y hábito tabáquico son coincidentes con los de otras series. Sin embargo, el porcentaje de pacientes diagnosticados en etapa de nódulo periférico es claramente menor a los registrados en países desarrollados (13 versus 50 por ciento). Este hecho muestra la importancia del tamizaje oportuno del paciente con CABA para encontrarlos en la etapa más precoz. La frecuencia de pacientes con CABA diagnosticados en etapa de nódulo periférico podría reflejar la calidad de la pesquisa del cáncer pulmonar en cualquier centro hospitalario