Juan Carlos Arango Viana

E280A PS-1 mutation causes Alzheimer's disease but age of onset is not modified by ApoE alleles

A single base substitution of a glutamic acid to an alanine codon 280 was found in the presenilin‐1 (PS‐1) gene on chromosome 14 in affected individuals in each of seven Colombian early‐onset Alzheimers disease (AD) kindreds. The mutation segregated with disease in kindreds tested. In the largest kindred (C2), the maximum two‐point lod score between the mutation and AD was Z = 8.14 at θ = 0. The presence of a single mutation and the common geographic origin, with all families from the state of Antioquia, suggest a founder effect in this population. This finding is supported by the observation of a rare haplotype inherited with AD in all kindreds. These kindreds form the largest collection of AD cases with the same PS‐1 mutation and the same educational, environmental, and ethnic background in which to study the phenotypic effect of putative risk factors, such as the ϵ4 allele of apolipoprotein E (ApoE) or head trauma. Of the few AD cases having a history of head trauma, the age of onset was not lowered. No effect of ApoE genotype on the age of onset was detected. Previous investigations of the effect of ApoE genotype on the age of onset were confounded by small patient numbers, familial clustering of ApoE genotypes, and combining data from unrelated families with different mutations. Hum Mutat 10:186–195, 1997.

Exploring epistasis in candidate genes for antisocial personality disorder

Objective To identify and characterize high-order gene-to-gene interactions in antisocial personality disorder (ASPD). Methods Participants for case–control study were selected from the inmate male population in Bellavista prison from Medellin. The study included 310 individuals with ASPD and 200 with no ASPD. Diagnoses were made according to a best-estimate procedure based on a semistructured interview (diagnostic interview for genetic studies 3.0). We genotyped some single-nucleotide polymorphisms in candidate genes with main serotonin pathway effects. The gene–gene interaction was examined using the multifactor dimensionality reduction method version 2.0.&agr;. We assessed model sizes of 2 and 3 loci and counted the number of replicates that contained the causal loci in the final best model that was identified using 10-fold cross validation. Results We find epistatic interaction with catechol-O-methyl transferase (COMT), tryptophan hydroxylase, and 5-HTR2A (serotonin receptor) with ASPD. This data supports an important role of polymorphism in serotonin receptors and low enzyme activity of COMT for susceptibility to ASPD. Conclusion This study suggests that gene interactions between genetic variants in COMT, 5-HTR2A and tryptophan hydroxylase gene would be associated with ASPD and influence the dopamine rewards pathways and modulate serotonin levels in ASPD.

Características de los suicidios de áreas rurales y urbanas de Antioquia, Colombia

Resumen Objetivo Determinar si existen diferencias entre areas rurales y urbanas de Antioquia en las caracteristicas asociadas con el suicidio. Metodo Se compararon 79 sujetos provenientes de areas rurales y 75 de areas urbanas de Antioquia. Se hizo autopsia psicologica y se calcularon razones de prevalencia (RP) (frecuencia de la caracteristica en zona rural/frecuencia de la caracteristica en zona urbana). Resultados Las caracteristicas asociadas de manera independiente con provenir de area rural y urbana fueron: “momento del suicidio durante la noche” (RP = 0,65; IC 95%: 0,48–0,89) y “vivir solo” (RP = 0,40; IC 95%: 0,17–0,98), que fueron mas frecuentes en zona urbana, y “envenenamiento con pesticidas”, que ocurrio mas en zona rural (RP = 1,80; IC 95%: 1,39–2,34). Conclusiones Los individuos suicidas provenientes de zonas rurales y urbanas tenian caracteristicas diferentes. Ello puede tener implicaciones para el diseno de las estrategias de prevencion del suicidio en cada una de las zonas. Se requieren otros estudios para determinar los factores de riesgo propios de cada area.

Prevalencia de variantes en el gen de la apolipoproteína E (APOE) en adultos de la población general del área urbana de Medellín (Antioquia)

OBJECTIVE To determine the allelic and genotype frequencies of apolipoproteine E (APOE) gene in a representative sample of the adult population of Medellin in 2010. METHODS A representative sample of the adult population of Medellin, was obtained by means of a multi-stage, stratified, conglomerate based sampling method. APOE genotyping was carried out on each of the participants. The sampling design was taken into consideration for the frequencies and association analysis. RESULTS The frequencies of the APOE alleles E2, E3 and E4 were 3.9, 92.0 and 4.1%, respectively. The frequencies of the different APOE genotypes were as follows: 2/2, 0.2%; 2/3, 6.8%; 2/4, 0.6%; 3/3, 85.0%; 3/4, 7.2%, and 4/4, 0.3%. CONCLUSIONS The allelic and genotype frequencies of APOE in an adult population of Medellin did not differ substantially from other series reported in South America. These data are important to determine the real impact of APOE on the population risk of several psychiatric diseases.

Encefalitis por virus de inmunodeficiencia humana, reporte de un caso y revisión de tema

In this paper we describe the case of a patient with histological diagnosis of human immunodeficiency virus (HIV) encephalitis, which also had multiple co-infections. It is a striking case, because of the incidence of this disease has markedly decreased in the post Highly Active Antiretroviral Therapy HAART era. The patient was a heterosexual male of 63 years old engaged in risky sexual behavior, who was admitted to a reference hospital with respiratory symptoms. During hospitalization He was diagnosed with stage C3 HIV/AIDS, multiple infections such as Hepatitis B, Neurosyphilis, systemic cryptococcosis, cerebral toxoplasmosis, cutaneous histoplasmosis, oral herpes and candida infections; He received appropriate treatments for all of the above, however He died 27 days later by disseminated cryptococcosis. He underwent autopsy and in central nervous system in the white matter were observed numerous microglial nodules, perivascular lymphocytes and multinucleated giant cells without granuloma formation. These giant cells are characteristics of HIV encephalitis. This patient is an example of the natural history of HIV infection that progressed to an advanced stage of AIDS.

Angiopatía amiloide cerebral con inflamación relacionada y demencia rápidamente progresiva: primer reporte de caso en Colombia

Cerebral amyloid angiopathy (CAA) is the deposition of amyloid in the wall of intracranial blood vessels, and leads to the appearance of hemorrhage, ischemia or leukoencephalopathy. The clinical manifestations of the CAA are highly variable, such as cognitive impairment, behavioral abnormalities, focal neurological deficits, headache or seizures. A subtype, Cerebral amyloid angiopathy-related inflammation (CAA-RI) has recently been reported in the world literature. We report the case of a 74-year-old with a rapidly progressive dementia about three months duration, associated with headache, meningismus, decreased strength in right hemisphere, multiple parenchymal hemorrhagic lesions, diffuse hemosiderosis, cerebral edema focal and histological study with evidence of intracerebral amyloid. The diagnosis of CAA is based on a clinical history compatible, neuroimaging showing hemosiderosis or multiple bleeding, predominantly in posterior fossa, and in some cases histological examination to confirm the presence of amyloid in intracranial microcirculation. Modified Boston criteria, unify the findings for the diagnosis of CAA, with varying degrees of certainty. Sometimes, as in the case presented, the CAA is associated with an inflammatory component, and is manifested by a rapidly progressive dementia, becoming a true diagnostic challenge.

Artículo originalPrevalencia de variantes en el gen de la apolipoproteína E (APOE) en adultos de la población general del área urbana de Medellín (Antioquia)Prevalence of Variants in the Apolipoprotein E (APOE) Gene in a General Population of Adults from an Urban Area of Medellin (Antioquia)

OBJECTIVE To determine the allelic and genotype frequencies of apolipoproteine E (APOE) gene in a representative sample of the adult population of Medellin in 2010. METHODS A representative sample of the adult population of Medellin, was obtained by means of a multi-stage, stratified, conglomerate based sampling method. APOE genotyping was carried out on each of the participants. The sampling design was taken into consideration for the frequencies and association analysis. RESULTS The frequencies of the APOE alleles E2, E3 and E4 were 3.9, 92.0 and 4.1%, respectively. The frequencies of the different APOE genotypes were as follows: 2/2, 0.2%; 2/3, 6.8%; 2/4, 0.6%; 3/3, 85.0%; 3/4, 7.2%, and 4/4, 0.3%. CONCLUSIONS The allelic and genotype frequencies of APOE in an adult population of Medellin did not differ substantially from other series reported in South America. These data are important to determine the real impact of APOE on the population risk of several psychiatric diseases.