RESUMEN
This study was conducted in Posse, a rural community in Goiàs, Brazil. Persons were recruited into the study through house-to-house sampling of all houses in the sampled area. Blood samples were collected for seropositivity assessments for Trypanosoma cruzi and an electrocardiogram was assessed using a portable system. The results demonstrate significant differences between seropositive and seronegative persons for electrocardiographic (ECG)-derived traits. Seropositive persons had substantially longer QRS and QT intervals than seronegative persons. The PR interval was significantly different between seropositive and seronegative persons. Conduction abnormalities were observed more frequently in seropositive than seronegative persons. Right bundle branch block, an ECG abnormality typical of Chagas disease, was observed in 15% of seropositive persons compared with less than 1% of seronegative persons. Results indicate that T. cruzi infection and subsequent Chagas disease will continue to be major health problems for the foreseeable future in this typical rural area of Brazil.
Asunto(s)
Enfermedad de Chagas/complicaciones , Enfermedad de Chagas/inmunología , Cardiopatías/complicaciones , Animales , Brasil , Enfermedad de Chagas/sangre , Electrocardiografía , Femenino , Humanos , Masculino , Trypanosoma cruzi/inmunologíaRESUMEN
The understanding of the role of the immune response in the development of gastrointestinal and cardio-digestive (CD) forms of Chagas disease has received little attention. In this paper, the commitment of each leukocyte population of peripheral blood to the production of IFN-gamma, TNF-alpha, IL-12, IL-4, IL-5 and IL-10 was studied in patients with the CD form of Chagas disease. The data show that cells from patients with the CD form of the disease have distinct cytokine profiles when compared with the other clinical forms of Chagas disease and suggest that eosinophils are the major source of cytokine production in this clinical entity. The data presented in this paper demonstrate that patients with CD form can be distinguished from patients with gastrointestinal or cardiac forms of the disease by the distinct cytokine profile of peripheral blood cells.
Asunto(s)
Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/patología , Adulto , Anciano , Animales , Células Cultivadas , Enfermedad de Chagas/metabolismo , Citocinas/metabolismo , Eosinófilos/metabolismo , Eosinófilos/parasitología , Femenino , Humanos , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Interleucina-4/metabolismo , Interleucina-5/metabolismo , Leucocitos/metabolismo , Leucocitos/parasitología , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Fenotipo , Trypanosoma cruzi/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: We conducted a whole-genome, multipoint linkage screen to localize a previously reported major locus accounting for 56% to 67% of the additive genetic effects on covariate-adjusted plasma HDL cholesterol (HDL-C) levels in Mexican Americans from the San Antonio Family Heart Study (SAFHS). METHODS AND RESULTS: After using complex segregation analysis to recover the major locus in 472 SAFHS participants from 10 genotyped families, we incorporated covariates required to detect that major locus, including plasma levels of triglycerides and apolipoprotein A-I, in a maximum-likelihood-based variance-components linkage screen. Only chromosome 16 exhibited convincing evidence for a quantitative trait locus (QTL), with a peak multipoint log of the odds (LOD)=3.73 (P=0.000034). Subsequent penetrance model-based linkage analysis, incorporating genotypes at the marker locus nearest the multipoint peak (D16S518) into the segregation model, detected linkage with the previously detected major locus (LOD=2.73, P=0.000642). Initial estimates place this QTL within a 15-cM region of chromosome 16q near the structural loci for lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP). CONCLUSIONS: A QTL influencing plasma levels of HDL-C in Mexican Americans from San Antonio maps to a region of human chromosome 16q near LCAT and CETP.
Asunto(s)
HDL-Colesterol/sangre , Cromosomas Humanos Par 16/genética , Americanos Mexicanos/genética , Sitios de Carácter Cuantitativo/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Apolipoproteína A-I/sangre , Marcadores Genéticos/genética , Pruebas Genéticas/métodos , Pruebas Genéticas/estadística & datos numéricos , Genoma Humano , Genotipo , Humanos , Escala de Lod , Masculino , Americanos Mexicanos/estadística & datos numéricos , Persona de Mediana Edad , Fenotipo , Texas/epidemiología , Triglicéridos/sangreRESUMEN
Trypanosoma cruzi (Schyzotrypanum, Chagas, 1909), and Chagas disease are endemic in captive-reared baboons at the Southwest Foundation for Biomedical Research, San Antonio, Texas. We obtained PCR amplification products from DNA extracted from sucking lice collected from the hair and skin of T. cruzi-infected baboons, with specific nested sets of primers for the protozoan kinetoplast DNA, and nuclear DNA. These products were hybridized to their complementary internal sequences. Selected sequences were cloned and sequencing established the presence of T. cruzi nuclear DNA, and minicircle kDNA. Competitive PCR with a kDNA set of primers determined the quantity of approximately 23.9 +/- 18.2 T. cruzi per louse. This finding suggests that the louse may be a vector incidentally contributing to the dissemination of T. cruzi infection in the baboon colony.
Asunto(s)
Vectores de Enfermedades , Infestaciones por Piojos/veterinaria , Papio/parasitología , Phthiraptera/parasitología , Trypanosoma cruzi/aislamiento & purificación , Animales , ADN de Cinetoplasto/análisis , ADN Protozoario/análisis , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena de la Polimerasa , Trypanosoma cruzi/genéticaRESUMEN
Recent changes in lifestyle have led to a global epidemic of obesity. To determine the associations of these changes with cardiovascular disease (CVD) risk, the authors correlated changes in CVD risk factors with changes in weight and physical activity in a population-based sample of 539 Mexican Americans in the San Antonio Heart Study in 1992-1999 who were examined twice approximately 5 years apart. Average weight change during that interval was 2.7 kg. While change in physical activity (expressed as percent change) was associated modestly only with change in low density lipoprotein cholesterol median diameter (p = 0.017), weight change was strongly and positively associated with unfavorable changes in lipid and lipoprotein traits, insulin levels, and blood pressure, explaining 2-10% of the variation in the risk factor changes during the interval. The unfavorable associations with weight gain tended to be more pronounced in lean compared with obese individuals and in men compared with women. However, the associations were significant for most CVD risk factors in all groups. In Mexican Americans, a population at high risk for obesity, weight change was positively correlated with metabolic variables associated with risk of CVD. Therefore, increasing adiposity in this population may tend to slow, or even reverse, the decline in CVD morbidity and mortality.
Asunto(s)
Peso Corporal , Enfermedades Cardiovasculares/epidemiología , Americanos Mexicanos/estadística & datos numéricos , Esfuerzo Físico , Adulto , Análisis de Varianza , Glucemia/análisis , Índice de Masa Corporal , Enfermedades Cardiovasculares/sangre , Femenino , Humanos , Modelos Lineales , Lípidos/sangre , Masculino , Factores de Riesgo , Distribución por Sexo , Texas/epidemiología , Factores de Tiempo , Población Urbana/estadística & datos numéricosRESUMEN
Chagas' disease remains a major public health concern throughout much of Latin America. In Brazil, segments of the population experience Trypanosoma cruzi infection rates as high as 65%, indicating that control programs are still needed. Few data are available concerning people's health beliefs related to Chagas' disease in heavily infected populations. Such health beliefs may significantly impact the effectiveness of intervention schemes. The purpose of this study was to assess health beliefs related to Chagas' disease in a population experiencing infection high rates with the causal parasite. The focal population for the study consisted of the residents of Posse, a rural community in the State of Goiás. The results indicate that a majority of the population had a high degree of knowledge about Chagas' disease and the vector involved in its transmission. These findings indicate that control programs conducted by the Brazilian Ministry of Health have included effective educational components.
Asunto(s)
Enfermedad de Chagas , Conocimientos, Actitudes y Práctica en Salud , Adolescente , Adulto , Factores de Edad , Anciano , Brasil/epidemiología , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/prevención & control , Niño , Preescolar , Educación en Salud , Humanos , Lactante , Recién Nacido , Entrevistas como Asunto , Persona de Mediana Edad , Población RuralRESUMEN
Chagas' disease is a zoonotic disease found throughout Latin America. Despite control programs in many of the affected countries, infection with Trypanosoma cruzi continues to be a major public health concern. In Brazil alone, approximately 53 million people live in endemic areas. Research with humans and with animal models indicates that there is variation in susceptibility to infection with T. cruzi. The reasons for this variation are not known although several studies have implicated genetic factors. An indirect immunofluorescence assay was used to assess seropositivity for T. cruzi infection in 716 adults from the municipality of Posse, Goias, Brazil. Detailed genealogic information was gathered at the time of sampling, which allowed assignment of 525 individuals to 146 pedigrees containing between two and 103 individuals; the remaining 191 unrelated individuals were retained as independents in the analysis. Using a maximum likelihood variance decomposition approach, we performed quantitative genetic analyses to determine if genetic factors could partially account for the observed pattern of seropositivity. The maximum likelihood estimate of the heritability of T. cruzi infection was 0.56 +/- 0.27 (mean +/- SE), indicating that genetic factors account for more than half of the observed variation in infection status. An additional 23% of the variation (c2 = 0.23 +/- 0.09) is attributable to the effects of shared environment, as assessed by common household. The results indicate that genetic factors play an important role in determining epidemiologic patterns of T. cruzi infection. Further characterization of these genetic factors may suggest new biologic areas to be targeted by prevention and intervention programs.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Enfermedad de Chagas/genética , Trypanosoma cruzi/inmunología , Adolescente , Adulto , Factores de Edad , Anciano , Animales , Brasil/epidemiología , Enfermedad de Chagas/epidemiología , Niño , Preescolar , Humanos , Lactante , Persona de Mediana Edad , PrevalenciaRESUMEN
The purpose of this study was to investigate the genetic control of various HDL measures and to determine the proportion of genetic variance explained by shared genes (ie, pleiotropy) and the proportion unique to each trait. The data used were drawn from large, randomly ascertained pedigrees of Mexican Americans participating in the San Antonio Family Heart Study. Data were available for 655 individuals (258 men and 397 women) in 26 families. We performed a multivariate quantitative genetic analysis to simultaneously estimate both the additive genetic and random environmental correlations among seven HDL phenotypes. These seven HDL phenotypes can be divided into two categories: measures of concentration and estimates of particle size. Concentration was measured for apo A-I, apo A-II, esterified cholesterol, and unesterified cholesterol, and particle size was estimated for apo A-I, apo A-II, and esterified cholesterol. The heritabilities (h2) for each of the seven traits were significantly greater than zero (P<.05) and ranged from 0.2 to 0.6. When considered in a pairwise fashion, all combinations of these traits showed marked genetic correlations (rho(G)=0.33 to 0.87) and all were significantly greater than zero (P<.05), indicative of pleiotropic effects. However, we found substantial unique genetic variance for each of these traits even after accounting for the effects shared in common with all the remaining measures. We conclude that the genetic variation in these HDL phenotypes is a result of the action of common as well as unique genes.
Asunto(s)
Lipoproteínas HDL/genética , Fenotipo , Adulto , Apolipoproteína A-I/análisis , Apolipoproteína A-II/análisis , Colesterol/sangre , Ésteres del Colesterol/sangre , HDL-Colesterol/sangre , HDL-Colesterol/genética , Femenino , Hispánicos o Latinos , Humanos , Lipoproteínas HDL/sangre , Masculino , México/etnología , Tamaño de la PartículaRESUMEN
Analyses of 1163 samples from the San Antonio Family Heart Study revealed several elements of genetic control of lipoprotein(a) (Lp(a)) concentrations in Mexican Americans. Apolipoprotein(a) (apo(a)) isoform size variation was inversely related to Lp(a) concentrations and explained about 22% of total phenotypic variation. Segregation analyses suggested the existence of a major gene that influenced an additional 41% of total Lp(a) variation. A G-->A polymorphism in the LPA promoter was in strong disequilibrium with apo(a) isoform size, but did not contribute a significant amount of additional information about Lp(a) variation. However, about 25% of variation in Lp(a) concentrations was influenced by additive polygenic effects, which include the effects of null phenotype alleles. Altogether, these genetic components explained 89% of Lp(a) variation, similar to heritability estimates made in several other studies. Apo(a) size variation and the major gene (explaining a total of about 62% of Lp(a) variation) were linked to each other and, as expected, to the plasminogen locus. Thus, together with the well-established null phenotype allele, these different genetic factors represent at least three distinct elements of control exerted at the LPA locus, which encodes the apo(a) protein.
Asunto(s)
Apolipoproteínas/genética , Mapeo Cromosómico , Ligamiento Genético , Lipoproteína(a)/sangre , Lipoproteína(a)/genética , Americanos Mexicanos/genética , Adulto , Apoproteína(a) , Femenino , Genes , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Concentración Osmolar , Polimorfismo Genético , Regiones Promotoras GenéticasRESUMEN
BACKGROUND: The familial aggregation of coronary heart disease can be in large part accounted for by a clustering of cardiovascular disease risk factors. To elucidate the determinants of cardiovascular disease, many epidemiological studies have focused on the behavioral and lifestyle determinants of these risk factors, whereas others have examined whether specific candidate genes influence quantitative variation in these phenotypes. METHODS AND RESULTS: Among Mexican Americans from San Antonio (Tex), we quantified the relative contributions of both genetic and environmental influences to a large panel of cardiovascular risk factors, including serum levels of lipids, lipoproteins, glucose, hormones, adiposity, and blood pressure. Members of 42 extended families were studied, including 1236 first-, second-, and third-degree relatives of randomly ascertained probands and their spouses. In addition to the phenotypic assessments, information was obtained regarding usual dietary and physical activity patterns, medication use, smoking habits, alcohol consumption, and other lifestyle behaviors and medical factors. Maximum likelihood methods were used to partition the variance of each phenotype into components attributable to the measured covariates, additive genetic effects (heritability), household effects, and an unmeasured environmental residual. For the lipid and lipoprotein phenotypes, age, gender, and other environmental covariates accounted in general for < 15% of the total phenotypic variance, whereas genes accounted for 30% to 45% of the phenotypic variation. Similarly, genes accounted for 15% to 30% of the phenotypic variation in measures of glucose, hormones, adiposity, and blood pressure. CONCLUSIONS: These results highlight the importance of considering genetic factors in studies of risk factors for cardiovascular disease.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Americanos Mexicanos , Adulto , Factores de Edad , Anciano , Antropometría , Apolipoproteínas A/sangre , Glucemia , Presión Sanguínea , Enfermedades Cardiovasculares/complicaciones , HDL-Colesterol/sangre , Sulfato de Deshidroepiandrosterona/sangre , Complicaciones de la Diabetes , Diabetes Mellitus/epidemiología , Salud de la Familia , Femenino , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Prevalencia , Factores de Riesgo , Factores Sexuales , Globulina de Unión a Hormona Sexual/metabolismo , Texas/epidemiologíaRESUMEN
We investigated the effects of apolipoprotein (apo) B signal peptide length polymorphisms on low density lipoprotein cholesterol (LDL-C), apo B, and post-challenge (2 h) glucose levels in 686 Mexican Americans from 34 families. The most common allele encoded an apo B signal peptide of 27 amino acids (ins; SP-27), the next most frequent allele encoded a 24 amino acid signal peptide (del; SP-24), and the rarest allele encoded a 29 amino acid signal peptide (ins; SP-29) that has been found only in Mexican Americans. Homozygotes for the SP-24 allele had significantly higher mean levels of apo B. LDL-C, and 2-h glucose than SP-27 homozygotes, and SP-27/SP-24 heterozygotes had intermediate levels (P = 0.01 for apo B, P < 0.001 for LDL-C, and P = 0.04 for 2-h glucose). Heterozygotes for the SP-29 allele had higher apo B and LDL-C levels compared to homozygotes for the SP-27 or SP-24 alleles. Apo B signal peptide length polymorphism accounted for 4.2%, 3.5%, and 3.0% of the residual variation in LDL-C, apo B, and 2-h glucose levels, respectively, among the Mexican American families.
Asunto(s)
Apolipoproteínas B/genética , Glucemia/análisis , LDL-Colesterol/sangre , Americanos Mexicanos/genética , Polimorfismo Genético , Señales de Clasificación de Proteína/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/epidemiología , Alelos , Apolipoproteínas B/sangre , Arteriosclerosis/epidemiología , Arteriosclerosis/etnología , Secuencia de Bases , Grasas de la Dieta , Susceptibilidad a Enfermedades/etnología , Ingestión de Energía , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Esfuerzo Físico , Pobreza , Factores de Riesgo , Texas/epidemiologíaRESUMEN
We investigated the effects of non-insulin-dependent diabetes mellitus (NIDDM) on lipoprotein(a) (Lp[a]) and apolipoprotein(a) (apo[a]) in a population of Mexican-Americans. In plasma samples from 536 subjects, we measured Lp(a) concentrations, and we estimated apo(a) isoform sizes following immunostaining of plasma proteins resolved using sodium dodecyl sulfate electrophoresis. We identified 81 diabetic subjects who had 108 distinct apo(a) isoform bands. We then identified 81 nondiabetic subjects from the remainder who were closely matched for apo(a) phenotype (i.e., number and size of apo(a) isoform bands). As expected, the diabetic group had higher levels of glucose and insulin (both fasted and 2 h after glucose challenge) and triglycerides, and lower levels of high-density lipoprotein (HDL) cholesterol when compared with the matching nondiabetic group. Moreover, the diabetic group also had significantly lower Lp(a) concentrations than the nondiabetic subjects (10.6 vs. 13.6 mg/dl, P = 0.045) using a paired Student's t test. To detect the effects of diabetes on apo(a) size, we identified by pedigree analysis the nondiabetic family members who possessed alleles identical to those in the diabetic group. When we compared the average sizes for each allele, we found that apo(a) isoforms averaged 4.1 kDa larger in diabetic subjects than the genetically identical apo(a) measured in nondiabetic subjects (P = 0.044, n = 36 alleles). In summary, we have detected significant effects of NIDDM both on Lp(a) concentrations and on apo(a) size.
Asunto(s)
Apolipoproteínas/metabolismo , Diabetes Mellitus Tipo 2/sangre , Lipoproteína(a)/sangre , Apolipoproteínas/análisis , Apoproteína(a) , Glucemia/análisis , Enfermedades Cardiovasculares/epidemiología , Colesterol/sangre , HDL-Colesterol/sangre , Femenino , Hispánicos o Latinos , Humanos , Insulina/sangre , Masculino , México/etnología , Persona de Mediana Edad , Distribución Aleatoria , Valores de Referencia , Factores de Riesgo , TexasRESUMEN
Antithrombin III polymorphism was observed in the gray short-tailed opossum, Monodelphis domestica, by either one-dimensional polyacrylamide gel electrophoresis (PAGE; pH 7.9), two-dimensional PAGE (agarose, pH 5.4; 12% T, pH 7.9), or isoelectric focusing (pH 4.2-4.9) followed by immunoblotting with rabbit antiserum to human antithrombin III. Family studies demonstrated an inheritance of three codominant autosomal alleles, AT3A, AT3B, and AT3C, and a population study revealed frequencies of 0.70, 0.10, and 0.20, respectively.
Asunto(s)
Antitrombina III/genética , Zarigüeyas/genética , Polimorfismo Genético , Alelos , Animales , Antitrombina III/aislamiento & purificación , Electroforesis de las Proteínas Sanguíneas , Brasil , Electroforesis en Gel Bidimensional , Electroforesis en Gel de Poliacrilamida , Frecuencia de los Genes , Immunoblotting , Focalización Isoeléctrica , Zarigüeyas/sangreRESUMEN
The gray short-tailed opossum, Monodelphis domestica, is a model species for studying the underlying mechanisms that govern recombination. We have identified a new marker, PI (protease inhibitor), in M. domestica and demonstrate its linkage to AK1 (adenylate kinase 1). The rate of recombination in females of this species is approximately one fifth the rate in males, as might be predicted from the difference in chiasma frequency between the two sexes.