Polimorfismo T174M del gen del angiotensinógeno: relaciones opuestas con la hipertensión arterial esencial y con la obesidad en una población homogénea de Mallorca (Islas Baleares) / Angiotensinogen gene t174m polymorphism: opposite relationships with essential hypertension and obesity in a homogeneous population from Majorca (Baleric Islands, Spain)

Los estudios de asociación que se han realizado para investigar la relación delgen del angiotensinógeno con la hipertensión han dado resultados conflictivos debido,entre otras razones, a la heterogeneidad genética y fenotípica de las poblacionesestudiadas. Por otra parte, la hipertensión es un problema sanitario de notableimportancia cuantitativa en las Islas Baleares. Por estas razones hemosrealizado un estudio de asociación de los polimorfismos dialélicos M235T, T174My G-6A del gen del angiotensinógeno con la hipertensión, utilizando una muestrade población de Mallorca (Islas Baleares) de una considerable homogeneidadétnica y ambiental, constituida por 109 pacientes y 107 controles. Los alelos sedeterminaron mediante reacción en cadena de la polimerasa y análisis de sitiosde restricción. La asociación genotipos-variables dependientes se valoró medianteanálisis de regresión logística simple y multivariante. Sólo tras el ajuste por obesidad,historia familiar de hipertensión y diabetes hubo una tendencia a la asociaciónentre el genotipo T174T174 y la hipertensión, que alcanzó el límite de lasignificación estadística [OR = 2,76 (intervalo de confianza del 95%: 1,00-7,65,p = 0,05)]. Sin embargo hubo una asociación negativa significativa del genotipoT174T174 con la obesidad, tanto en el análisis simple [OR = 0,41 (intervalo deconfianza del 95%: 0,18-0,90, p = 0,03)] como tras el ajuste por sexo, hipertensióny diabetes [OR = 0,26 (intervalo de confianza del 95%: 0,10-0,65, p =0,004)]. Nuestros resultados discrepan de la opinión más extendida de que es elalelo M174 el que eventualmente se asocia a hipertensión. A la vista de los mismosse enfatiza la necesidad de controlar rigurosamente la obesidad en los estudiosde asociación del gen del angiotensinógeno con la hipertensión, y se aconsejael uso de poblaciones concretas para llevar a cabo los estudios acerca de lagenética molecular de la hipertensión

Numerous association studies have been performed to evaluate the relationshipbetween the angiotensinogen gene and the essential hypertension, but their resultsare conflicting. The conflicting results may be explained by methodological reasons,particularly genetic differences in the population samples, phenotypic differencesin the hypertensive populations analyzed, lack of appropriate control forother hypertension risk factors in some studies, or limited statistical power amongmany studies. Furthermore, hypertension is a public health issue of great relevancein Baleric Islands (Spain). For these reasons we performed an association studyabout the relationship between the M235T, T174M and G-6A diallelic polymorphismsof the angiotensinogen gene and hypertension in a population from Majorca(Balearic Islands), in which a considerable homogeneity with respect to ethnicityand environmental factors could be documented. This population wascomposed of 109 patients and 107 controls. Alleles of the angiotensinogen genewere determined by PCR and restriction site polymorphism analysis. The differentgenotypes were tested for association with dependent variables by univariate andmultivariate logistic regression analysis. In the univariate analysis we found no evidenceof association between the angiotensinogen gene genotypes and hypertension.This lack of association was independent of obesity, familial history of hypertensionand diabetes for the genotypes of the polymorphisms M235T and G-6A;however, in the multivariate analysis the T174T174 genotype showed an almostsignificant positive association with hypertension [OR = 2.76 (95% confidence interval:1.00-7.65, p = 0.05)]. The T174T174 genotype also showed a significantnegative association with obesity [OR = 0.41 (95% confidence interval: 0.18-0.90,p = 0.03)] that remained after adjustment by sex, hypertension and diabetes [OR= 0.26 (95% confidence interval: 0.10-0.65, p = 0.004)]. Our results: a) are incontrast with the results from most previous studies that found a relationship ofthe T174M polymorphism with hypertension, as in those studies the M174 allelewas responsible for the association; b) emphasize the need for rigorous controlfor obsesity in the studies of association between the angiotensinogen gene andhypertension; c) underscore the importance and the utility of using concrete populationsto carry out studies on the genetic dissection of hypertension

Association of HLA-DRB3*0202 and serum IgG antibodies to Chlamydia pneumoniae with essential hypertension in a highly homogeneous population from Majorca (Balearic Islands, Spain).

Separate studies investigating the relationship of essential hypertension (EH) with the HLA system and with Chlamydia pneumoniae (C. pneumoniae) infection have given conflicting results. Our aim was to clarify these relationships and determine whether the HLA system and C. pneumoniae infection interact with respect to the risk for EH. An association study (110 essential hypertensives and 107 controls) was conducted in a highly homogeneous population in the Balearic Island of Majorca (Spain). Molecular typing of HLA-B and HLA-DRB and quantification of serum levels of IgG antibodies to C. pneumoniae (sIgGa-Cp) were determined. Student's t-test, chi(2)-statistics, logistic regression analysis, and general linear model ANOVA were used for statistical analysis. The results showed that EH was related with HLA-DRB3*0202 in the whole study population, and with levels of sIgGa-Cp>63.5 BU/ml in the group of individuals with sIgGa-Cp>30 BU/ml (OR (95% CI) adjusted for obesity, familial history of EH and diabetes=2.06 (1.07-3.97), P=0.03, and =4.60 (1.06-19.90), P=0.04, respectively). The association between EH and sIgGa-Cp was observed in the DRB3*0202(+) individuals, but not in the DRB3*0202(-) subgroup (OR (95% CI)=11.14 (1.92-64.54), P=0.004, and =0.98 (0.22-4.43), P=0.64, respectively (P of the Mantel-Haenszel test for homogeneity of OR=0.06)). In our population, EH was positively associated with HLA-DRB3*0202 and with high levels of sIgGa-Cp. Moreover, a significant interaction of DRB3*0202 on the effect of sIgGa-Cp was observed, as the association of EH with these antibodies depended on the presence of DRB*0202.

[Angiotensinogen gene T174M polymorphism: opposite relationships with essential hypertension and obesity in a homogeneous population from Majorca (Baleric Islands, Spain)]. / Polimorfismo T174M del gen del angiotensinógeno: relaciones opuestas con la hipertensión arterial esencial y con la obesidad en una población homogénea de Mallorca (Islas Baleares).

Numerous association studies have been performed to evaluate the relationship between the angiotensinogen gene and the essential hypertension, but their results are conflicting. The conflicting results may be explained by methodological reasons, particularly genetic differences in the population samples, phenotypic differences in the hypertensive populations analyzed, lack of appropriate control for other hypertension risk factors in some studies, or limited statistical power among many studies. Furthermore, hypertension is a public health issue of great relevance in Baleric Islands (Spain). For these reasons we performed an association study about the relationship between the M235T, T174M and G-6A diallelic polymorphisms of the angiotensinogen gene and hypertension in a population from Majorca (Balearic Islands), in which a considerable homogeneity with respect to ethnicity and environmental factors could be documented. This population was composed of 109 patients and 107 controls. Alleles of the angiotensinogen gene were determined by PCR and restriction site polymorphism analysis. The different genotypes were tested for association with dependent variables by univariate and multivariate logistic regression analysis. In the univariate analysis we found no evidence of association between the angiotensinogen gene genotypes and hypertension. This lack of association was independent of obesity, familial history of hypertension and diabetes for the genotypes of the polymorphisms M235T and G-6A; however, in the multivariate analysis the T174T174 genotype showed an almost significant positive association with hypertension [OR = 2.76 (95% confidence interval: 1.00-7.65, p = 0.05)]. The T174T174 genotype also showed a significant negative association with obesity [OR = 0.41 (95% confidence interval: 0.18-0.90, p = 0.03)] that remained after adjustment by sex, hypertension and diabetes [OR = 0.26 (95% confidence interval: 0.10-0.65, p = 0.004)]. Our results: a) are in contrast with the results from most previous studies that found a relationship of the T174M polymorphism with hypertension, as in those studies the M174 allele was responsible for the association; b) emphasize the need for rigorous control for obsesity in the studies of association between the angiotensinogen gene and hypertension; c) underscore the importance and the utility of using concrete populations to carry out studies on the genetic dissection of hypertension.

[How can we improve mortality records in primary care?]. / 'Cómo podemos mejorar el registro de mortalidad en la atención primaria?

OBJECTIVE: To calculate whether the introduction for systematic use of an epicrisis form for deaths improved the quality of mortality records in a primary care centre (PCC). DESIGN: Before and after study. SETTING: Urban, with a population of 31 000. Patients and other participants. All the deaths recorded at the PCC before 1996 (N=396) and in the period from January 1999 to August 2000 (N=160). MAIN MEASUREMENTS AND RESULTS: The number of deaths recorded at the PCC represents only 32.5% of the official data obtained from the municipal registry in the 1996 evaluation, and 51.5% in the 2000 evaluation. In 2000 the epicrisis forms were filled out in 76.8% (95% CI, 65.0-88.6%) of all deaths. In the 1996 evaluation the place of death was not recorded in 65.5% (95% CI, 59.0-71.8%) of cases, but in 2000 this figure was 22.5% (95% CI, 19-26%). Undefined causes of death dropped from 37% (95% CI, 33.4-40.6%) in 1996 to 30.5% (95% CI, 25.8-35.2%) in 2000. Recording of cause of death rose from 64% (95% CI, 57.8-70.4%) in 1996 to 73% (95% CI, 61.8-84.4%) in 2000. CONCLUSIONS: Official data reveal under-recording of mortality at the PCC. The introduction of an epicrisis form for deaths has improved the quality of the centres mortality records.

¿Cómo podemos mejorar el registro de mortalidad en la atención primaria? / How can we improve mortality records in primary care?

Objetivo. Estimar si la implantación sistemática de una hoja de epicrisis para las defunciones mejora la calidad del registro de mortalidad en un centro de atención primaria (CAP).Diseño. Estudio antes-después. Emplazamiento. Urbano. Población: 31.000 habitantes. Pacientes u otros participantes. Todas las defunciones registradas en el CAP antes de 1996 (n = 396) y en el período comprendido entre enero de 1999 y agosto de 2000 (n = 160).Mediciones y resultados principales. El número de defunciones que constan en el CAP suponen un 32,5 por ciento respecto a los datos oficiales obtenidos del registro municipal para la evaluación de 1996 y un 51,5 por ciento para la evaluación de 2000. En el año 2000 las hojas de epicrisis constaban en un 76,8 por ciento (IC del 95 por ciento, 65,0-88,6 por ciento) de todas las defunciones. Comparando con la evaluación del año 1996 no constaba el lugar de la defunción en un 65,5 por ciento (IC del 95 por ciento, 59,0-71,8 por ciento) de los casos respecto al 22,5 por ciento (IC del 95 por ciento, 19-26 por ciento) de 2000. El porcentaje de causas de muerte indefinidas pasa del 37 por ciento (IC del 95 por ciento, 33,4-40,6 por ciento) en 1996 a un 30,5 por ciento (IC del 95 por ciento, 25,8-35,2 por ciento) en 2000. El porcentaje de registro de la causa de muerte pasa del 64 por ciento (IC del 95 por ciento, 57,8-70,4 por ciento) en 1996 al 73 por ciento (IC del 95 por ciento, 61,8-84,4 por ciento) en 2000.Conclusiones. Infrarregistro de mortalidad en el CAP en relación con los datos oficiales. La implantación de una hoja de epicrisis para las defunciones mejora la calidad del registro de mortalidad del centro (AU)

El gen del angiotensinógeno en la hipertensión arterial esencial / Angiotensinogen gene in human essential hypertension

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West Mediterranean islands (Corsica, Balearic islands, Sardinia) and the Basque population: contribution of HLA class I molecular markers to their evolutionary history.

The genetic structure of Balearic islands (Corsica and Sardinia), situated on the same trans-Mediterranean maritime routes and having very similar histories, were compared and their position among the neighbouring Caucasian populations was inferred. For this purpose, three HLA loci (HLA-A, -B and -Cw) were typed at the DNA level in these populations and the allelic and haplotypic frequencies were estimated. Because previous studies have shown common genetic features in the Sardinians and Basques, HLA-Cw molecular typing was also performed in a sample of French Basques in order to establish the haplotypic structure of this population for a more accurate comparison with the three others. By its allelic composition, the Corsican population has an intermediate position between the two other islander populations. Its close relationship with the Sardinian population, however, was clearly revealed by the phylogenetic analysis which also suggests a proximity with eastern Mediterranean peoples, whereas the Balearic islands are more narrowly related to Spain and western Europe. Peculiarities were observed in the distributions of some common haplotypes in the populations of the islands that confirm the results of the phylogenetic analysis and could be related to their history. Noteworthy is the presence of the HLA-A30-Cw*0501-B18 haplotype at frequencies approximately 2% in Corsica and the Balearic islands, yet the estimated frequencies of this haplotype are much lower than in the Sardinian and Basque populations.

[Intrathecal synthesis of IgG evaluated using different formulas: importance of multivariate analysis in the diagnosis of multiple sclerosis]. / Síntesis intratecal de IgG valorada mediante diferentes fórmulas: interés del análisis multivariante para el diagnóstico de esclerosis múltiple.

INTRODUCTION: Synthesis of IgG is useful data for the diagnosis of multiple sclerosis, and different formulas, both direct and indirect, are used to quantify this. We analyze these formulas with the objective of finding whether certain combinations of them would give better results than the individual formulas on their own. PATIENTS AND METHODS: We studied the cerebrospinal fluid of 45 patients with neurological disorders and determined the results of the two formulas which are most effective, according to some studies (Reiber's formula and IgG index) together with a direct formula (IgG ratio) and another indirect formula (the 'classical' formula of Tourtellotte). RESULTS: The IgG index was, in general, the formula which best differentiated between patients with multiple sclerosis and persons with other neurological disorders. CONCLUSIONS: We found a tendency which supported the original hypothesis that it is possible to use combinations of formulas to obtain better results than individual formulas. This fact may serve as a basis for further studies in which different combinations are tested, including analytical and clinical data, and this may be of use in the diagnosis of multiple sclerosis.

Síntesis intratecal de IgG valorada mediante diferentes fórmulas:interés del análisis multivariantepara el diagnóstico de esclerosis múltiple / Intrathecal synthesis of IgG evaluated using different formulas: the use of multivariate analysis for the diagnosis of multiple sclerosis

Introducción. La síntesis de IgG es un dato útil en el diagnóstico de esclerosis múltiple, y para cuantificarla se emplean diferentes fórmulas, directas o indirectas. Analizamos dichas fórmulas con el objetivo de ver si existen combinaciones de las mismas con mejor rendimiento que las individuales. Pacientes y métodos. Hemos estudiado el líquido cefalorraquídeo en 45 pacientes con enfermedades neurológicas y hemos determinado los resultados de las dos fórmulas que, según algunos trabajos, son más eficaces (fórmula de Reiber e índice de IgG), junto con una fórmula directa (ratio de IgG) y otra fórmula indirecta (la `clásica' de Tourtellotte). Resultados. El índice de IgG fue la fórmula que presentó la capacidad más alta para discriminar, en general, entre pacientes con esclerosis múltiple e individuos con otra enfermedad neurológica. Conclusiones. Encontramos una tendencia que apoya la hipótesis inicial de que es posible utilizar combinaciones de fórmulas que ofrezcan mejores rendimientos que las fórmulas individuales. Este hecho puede ser el punto de partida para otros estudios, en los que se prueben combinaciones diferentes, incluso de datos analíticos y clínicos, los cuales puedan mejorar nuestra capacidad para diagnosticar la esclerosis múltiple (AU)

Insulin-receptor interactions. Possible involvement of metals.

Addition of Zn2+ or Cu2+ ions to plasma membrane preparations or to purified insulin receptors from rat liver resulted in an increase of specific insulin binding; no effect was observed with the addition of Fe3+, Ca2+ or Na+. Dialysis of membrane preparations, or of purified receptors, against chelating agents such as zincon (2-carboxy-2'-hydroxy-5'-sulfoformazyl-benzene) or 1,10-phenantroline resulted in a decrease in specific binding of insulin. With the readdition of Zn2+ or Cu2+ to the medium an increase in specific binding was observed, and values much higher than those of the original preparations were obtained; the addition of Ca2+, Fe3+ or Na+ to dialyzed preparations did not cause any effect on the specific binding. Dialysis of purified receptors against chelating agents resulted in a decrease in the content of Zn2+ and Cu2+. Zincon has been found to be a competitive inhibitor of insulin interfering with the specific binding to the receptor, and noncompetitive with the nonspecific binding. These results suggest the possible involvement of a metal ion present in the receptor in the formation of the insulin-receptor complex.