A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD.

In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P<1 × 10(-8)) and 11q and 17p (P<1 × 10(-6)). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q-11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome.

[Dot blot for the diagnosis of porcine cysticercosis]. / Dot blot para el diagnóstico de la cisticercosis porcina.

The Taenia solium larva causes cysticercosis in pigs, as well as economic losses for farmers and taeniosis in humans, constituting a public health problem. Infested pigs must therefore be identified before they enter the food chain. To this end, a dot blot assay was developed for the immunodiagnosis of porcine cysticercosis. A study was made of 44 pigs from different areas of Colombia that had all tested positive to cysticercosis, both by necropsy and the Western blot technique. Another group was formed comprising 44 pigs that had all tested negative to Western blot and necropsy. After analysing these 88 samples to validate the diagnostic assay, the result was a sensitivity of 86.4% and a specificity of 93.2%. The dot blot assay proved useful in diagnosing porcine cysticercosis. As the assay is easy to use in laboratories in endemic areas, as well as under field conditions, it is also appropriate for epidemiological studies.

[Prevalence of Taenia solium antibodies in humans and in pigs in an endemic area of Colombia]. / Prevalencia de anticuerpos para Taenia solium en humanos y cerdos en una zona endémica colombiana.

INTRODUCTION: Cysticercosis (CC) caused by Taenia solium in humans and in pigs is endemic in many rural communities in developing countries. The use of Western blot assays (WB) to determine T. solium antibodies has become the best serological tool available to date for identifying positive individuals in field conditions. AIMS: The aim of this study was to determine the prevalence of T. solium antibodies in humans and in pigs in two rural communities in Antioquia, Colombia. PATIENTS, MATERIALS AND METHODS: Serological identification of humans and pigs with T. solium antibodies was performed using WB assays in two communities in Ituango, Antioquia. During the study, demographic variables, housing and health conditions were taken into account. Contingency tables were drawn up using c2 to compare the proportion of seronegative individuals and seropositive individuals with headache, fainting or convulsions. RESULTS: The prevalence of human and porcine CC obtained was 2.23 and 6.82% in Pascuita and 1.17 and 2.33% in Guacharaquero, both respectively. Of the 11 WB positive patients evaluated by imaging techniques, two individuals were found to have single calcifications in the TAC scan and RMI showed another to have an unspecified lesion. The prevalence of infection in humans and in pigs in two rural communities in the north of the district of Antioquia, Colombia, shows that CC is endemic and that steps must be taken to control it.

Multiple sclerosis in the tropics: genetic association to STR's loci spanning the HLA and TNF.

Clear evidence has been presented correlating gene polymorphisms at 6p21.3-21.4 (containing HLA and TNF) and the predisposition to acquire multiple sclerosis (MS). In a previous study, we found that polymorphisms at HLA DQAI were associated with being or not being predisposed to MS in individuals inhabiting the tropics, where the prevalence of MS is significantly lower than in subtropical areas. Here, we tested the hypothesis that polymorphisms at D6S276, D6S265, D6S273 and D6S291 microsatellite loci are in strong linkage disequilibrium with a major genetic factor predisposing to MS. These microsatellites span the 6p21.3 region with intervals of 5 cM establishing particular landmarks for the HLA and TNF loci. Thirty-five MS patients and 35 controls, age, sex, social, ethnically and geographically matched healthy individuals, were studied. After testing the fit of gene frequencies to the normal distribution and performing the correlation for multiple comparisons, we found significant differences among the case and the control frequencies for the allele 202 belonging to the marker D6S276 (Pc=0.00455) and for the allele 114 belonging to the marker D6S265 (Pc=0.0084). For these two alleles at different loci, we found higher frequencies in the cases than in the controls. A nonsignificant p value was found in testing the existence of linkage disequilibrium among the studied loci in the cases and in the controls. In conclusion, the current study adds evidence to the established association among polymorphisms of genes located at 6p21.3-21.4 and MS. Furthermore, because of the distribution of the tested microsatellite loci, the more probable critical region could be correlated with the TNF neighborhood.

[Prevalence of myasthenia gravis in Antioquia, Colombia]. / Prevalencia de miastenia grave en Antioquia, Colombia.

INTRODUCTION: Myasthenia gravis (MG), considered the commonest of all the illnesses that affect neuromuscular transmission, is a disorder in which the autoimmune system attacks the post synaptic acetylcholine receptor proteins in the end plate terminal; it is characterised by weakness and skeletal muscle fatigue, with no anomalies in reflexes, sensitivity or coordination. Epidemiological indicators, such as incidence and prevalence, are not known in Colombia. AIMS. To determine the prevalence of MG among the inhabitants of Antioquia, through the use of the capture recapture method. PATIENTS AND METHODS: The capture recapture method was used for two sources, the Instituto Neurológico de Antioquia and the Hospital Universitario San Vicente de Pa l, which are the most important institutions for the diagnosis of neurological diseases in Antioquia. MG prevalence was calculated using the following formula: p= n/N 105. We examined the data from the period between 1 July 1995 and 30 June 2000 with the aim of identifying subjects who fitted the profile of MG sufferers. RESULTS: General MG prevalence in Antioquia was 27.7 cases per million inhabitants (CI 95%= 23.2 32.2). The male/female ratio was 1:3.77. CONCLUSIONS: The estimated prevalence of MG is lower than that reported in United States and other temperate regions, where it varies between 60 and 150 cases per million. The prevalence of MG is low in Antioquia, as in other tropical areas

[Vascular hereditary dementia CADASIL type in Colombia. III. Linkage analysis to notch3 gene]. / Demencia vascular hereditaria tipo CADASIL en Colombia. III. Análisis de ligamiento a Notch3.

OBJECTIVE: To perform linkage analysis between the Short Tandem Repeats (STR) microsatellite markers D19S923, D19S929, D19S22, which are in strong genetic linkage to Notch3 gene in order to contrast the hypothesis that the vascular hereditary dementia phenotype described in a multigenerational extended pedigree from Colombia correspond to CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). Even we know that using techniques as the Single Strand Conformational Polymorphisms (SSCP) could determine mutations in Notch3, the rationality of this approach is that intronic variations could not be defined and that we are interested in determine if some forms of the clinical presentation and its phenotypic variability make part of CADASIL. INTRODUCTION: The CADASIL phenotype is caused by mutations in the Notch3 gene. Clinical features of CADASIL are: 1. Recurrent cerebra-vascular episodes; 2. Migraine history; 3. History of transitory ischemic attack and, 4. Behavior changes and dementia. MATERIAL AND METHODS: By using SIMLINK we showed that the extended genealogy had the enough power to detect significant LOD (logarithm of oods) score values when Notch3 was considered the disorder cause. Linkage analysis was carried out by using parametric and non parametrical methods. The Elston-Stewart general method was used as the parametrical analysis and the sib pair method as the non-parametrical one. We perform simulations changing the affection status codification by including as affected or not including those individuals with migraine. Furthermore, in order to detect the stability of the results, we changed the penetrance values, the genetic frequencies on both, the marker loci and the affection locus. RESULTS: The maximum pair-wise LOD score was 2.04 which was detected at the marker D19S23 with q= 0.11cM. This distance correspond exactly with the Notch3 location. That is 100 times more probable that there is linkage that there is not. In other words this probability could be explained as if the phenotype correspond to CADASIL than to other vascular dementia. The non parametric results were compatibles with the parametric ones. When the migraine symptom was considered as a part of the affected status, the LOD score values showed not linkage. CONCLUSIONS: The results of the linkage analysis to these STR microsatellite markers suggest that the vascular hereditary dementia phenotype described in this family correspond to CADASIL caused by a polymorphism on the Notch3 gene. On the contrary, these same results suggest that the migraine phenotype is not a part of the progressive dementia.

Neurocysticercosis in persons with epilepsy in Medellín, Colombia. The Neuroepidemiological Research Group of Antioquia.

PURPOSE: A prospective series of 643 persons with epilepsy attending a reference neurologic center in Medellín, Colombia, was examined by computed tomography (CT scan) or serology or both with the enzyme-linked immunoelectrotransfer blot assay (EITB) to assess the prevalence of Taenia solium cysticercosis. METHODS: All presenting patients were consecutively enrolled in the study. Five hundred forty-six persons underwent cerebral CT scans; 376 of them also had serum EITB performed. RESULTS: Prevalence of neurocysticercosis by CT scan was 13.92%. Overall prevalence of T. solium antibodies with EITB was 9.82%, but for those with late-onset epilepsy (onset after age 30 years), prevalence increased to 17.5% and 19% for those who originated from outside urban Medellín. Seroprevalence in individuals with mixed lesions (cysts and calcifications) was 88.2% and 64.10% in those with live cysts. Conversely, only 2.72% of persons with CT findings not related to neurocysticercosis had positive EITB tests. CONCLUSIONS: Our study shows that an important proportion of individuals with epilepsy have radiologic or serologic evidence of T. solium infection, suggesting that neurocysticercosis is an important etiology for epilepsy in Colombia.

Esclerosis múltiple: aproximación epidemiológico-genética en habitantes de Antioquia, Colombia. II: desequilibrio de ligamento al HLA DQÓ / Multiple sclerosis: an epidemiologycal approach in Antioquia, Colombia. II: Linkage desequilibrium to HLA, locus DQÓ

La discriminación y cuantificación de los componentes ambientales y genéticos en el desarrollo de esclerosis múltiple (EM) no se ha podido realizar. con la finalidad de acercarnos a la discriminación de dichos componentes, hemos analizado casos afectados de EM a partir de la comunidad paisa de Antioquia, Colombia, zona situada en el trópico; para detectar un posible desequilibrio de ligamiento al HLA, locus DQÓ, aspecto que revelaría la importancia del componente genético en el desarrollo de EM. Un análisis de contingencia entre las distribuciones genotípicas del HLA DQÓ de los casos y controles, usando el remuestreo de Monte Carlo para solucionar el problema del tamaño muestral que es inherente a las poblaciones con baja prevalencia de EM, reveló que existen diferencias significativas entre las dos distribuciones. La tendencia alélica observada fue de un incremento de los alelos 1.1., 1.2 y una disminución de los alelos 3 (con un p significativamente < de 0,05) y 4 en la población afectada. Los mismos resultados han sido descritos en otras poblaciones de origen caucasoide no localizadas en el trópico, lo cual puede indicar que este componente genético descrito en la población caucasoide se ha mantenido en la poblaciòn de enfermos con EM originarios de Antioquia y que continúa siendo importante para el desarrollo de la enfermedad