The dystrophinopathies in Costa Rica

A five-years long study aiming to describe the basic genetic epidemiology of the dystrophinopathies in Costa Rica recruited 31 patients with clinical symptoms of DMD/BMD at the National Children’s Hospital (HNN). This center is the obligate reference hospital of the national health system for genetic diseases, however, the geographic origin of the patients, a low percentage of deletions and a high proportion of de novo mutations found among them indicate that a significant ascertainment bias impedes a substantial scientific approach to confront and alleviate the problems posed by these severe diseases in Costa Rica. Rev. Biol. Trop. 52(3): 485- 490. Epub 2004 Dic 15.Un estudio de cinco anos tendiente a describir la epidemiologia genética básica de las distrofinopatias en Costa Rica detecto 31 pacientes con sintomatologia de DMD o de BMD en el Hospital Nacional de Niños (HNN), el centro de referencia del sistema nacional de salud para enfermedades hereditarias, sin embargo. la distribucion geográfica de los pacientes, un bajo porcentaje de lesiones y una muy elevada proporción de mutaciones de novo indican que un significante sesgo de averiguación impide estudio científico de riguroso tendiente a disminuir el impacto de estas enfermedades en Costa Rica.The project was supported by the University of Costa Rica,(Project No. 742-97-253) and by the National Children Hospital (FUCODOCSA)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biologí

Glaucoma in Costa RIca. Initial approaches

El glaucoma es la segunda causa de ceguera irreversible en el mundo. El componente genetico de algunos de los distintos tipos ha sido demostrado: seis loci (GLC1AGLC1F) y dos genes (TIGNMY0C y OPTN) se conocen. hasta ahora, como responsables de la aparicion de glauet)-- mas primarios de angulo abierto tanto del tipo juvenil (JOAG) como del tipo de adultos (COAG). Ademas, dos loci (GLC3A,GLC3B) y un gene (CYPIBI) se hen descubierto coma causal del tipu primariu congenito (PCG). Sc presenta una relaciort de los estudios geneticos iniciales sobre el glaucoma en Costa Rica. Nueve families: 1 con JOAG, 1 con PCG y 7 con COAG se estudiaron en bused de mutaciones en los genes conocidos. Una duplicaciOn de 10 ph, 1546-1555dupTCATGCCACC, en el gene CYPIBI, causa glaucoma en condicionhornocigraa cn una fatutliaconsaguinca con PCG. Esta mutation se ha encontrado en otros paises y origins un codon dc terminacion prematuro que codifica una proteins 140 aminoacidos mas cotta que la normal. En dos de las families eon COAG encondo tins variante inocua Arg76Lys en el exon I del gen TIGR/MYOC. Otros pacienies prescntaron. en el gene OPTN, dos variantes en la region codificarne (Thr34Thr. Met 9SLys) y 7 cambios intrOnicos. Una de las familia.; con COAG cumple con los requerimientos minimos parr tut anilisis de ligamicnto, por lo que sc utilizaron 379 marcadores microsateliticos pars mapear el gen causante de Is enfermedad. No sc obtuvieron valores LOD quc elaramente impliearan a alguna region criamosamica. La evidencia senala que el glaucoma hereditario en Costa Rica tiene una gran heterogeneidad gcnetica y que es muy posible que los estudios que se desarrollan vayan a descubrir nuevos genes involucrados en la patologiaGlaucoma is the second most frequent cause of irreversible blindness worldwide. Genetic factors have been implicated in the development of the disease. So far six loci (GLCIA-GLCIF) and two genes (TIGRIMYOC and OPTN) arc involved in the development of juvenile (JOAG) and adult onset or chronic primary open angle glaucoma (COAG), while two loci (GLC3A,GLC313) and one gene (CYPIB1) are known for primary congenital glaucoma (PCG). Here we summarize the results of the first genetic studies of glaucoma in Costa Rica. Nine families: 1 with JOAG, 1 with PCG and 7 with COAG were screened for mutations at the known genes. A 10 bp duplication, 1546-1555dupTCATGCCACC, at the CYP1B1 gene, causes, in homozygous stale, glaucoma in the consanguineous PCG family. This mutation has been found in different countries and generates an early stop codon that termitates protein synthesis 140 amino acids earlier than the normal allele. In exon 1 of the TIGIUMYOC the innocuous Arg76Lys variant was found in two of the COAG families. In the OPTN gene two variants in the coding region (Thr34Thr, Met 98Lys) and 7 intronic changes were found in other Costa Rican glaucoma patients. One of the COAL families was chosen for a genome scan with 379 microsatellitc markers and linkage analysis. LOD scores "suggestive" of linkage were obtained for several chromosomal regions. Evidence indicates that hereditary glaucoma in Costa Rica is highly heterogeneous and that further studies in the country will probably disclose some up to now unknown genes responsible for the diseaseUniversidad de Costa Rica Instituto de Investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Diet and Leukocyte Telomere Length in a Population with Extended Longevity: The Costa Rican Longevity and Healthy Aging Study (CRELES)

Elderly Costa Ricans have lower mortality rates compared to their counterparts from developed countries. Reasons for this survival advantage are not completely known. In the present study, we aimed to identify dietary factors associated with leukocyte telomere length (LTL), a marker of biologic aging, in the elderly population of Costa Rica. We conducted prospective analysis in 909 participants aged 60+ years from the Costa Rican Longevity and Healthy Aging Study (CRELES). We used a food frequency questionnaire to assess usual diet. We calculated dietary patterns using Principal Component Analysis (PCA). We used generalized linear models to examine the association of dietary patterns and food groups with leukocyte telomere length. We found two major dietary patterns explaining 9.15% and 7.18% of the total variation of food intake, respectively. The first dietary pattern, which represents a traditional Costa Rican rice and beans pattern, was more frequent in rural parts of the country and was positively associated with baseline LTL: (95% CI) = 42.0 base-pairs (bp) (9.9 bp, 74.1 bp) per one-unit increase of the traditional dietary pattern. In analysis of individual food groups, intake of grains was positively associated with baseline LTL: (95% CI) = 43.6 bp (13.9 bp, 73.3 bp) per one-serving/day increase of consumption of grains. Our results suggest that dietary factors, in particular a traditional food pattern, are associated with telomere length and may contribute to the extended longevity of elderly Costa Ricans.Universidad de Costa Rica/[]/UCR/Costa RicaNational Institutes of Health/[P30 AG012839]/NIH/Estados UnidosNational Institutes of Health/[R01 AG031716]/NIH/Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Centro Centroamericano de Población (CCP)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biologí

The STR polymorphism (AAAAT)n within the intron 1 of the tumor protein 53 (TP53) locus in 17 populations of different ethnic groups of Africa, America, Asia and Europe

artículo arbitrado -- Universidad de Costa Rica, Instituto de investigaciones en Salud. 2004The SIR (A.AAAT). within intron 1 of the TP53 Locus was screened in 17 populations from 3 main ethnic groups: Europeans, Asiatics, and Africans. and from the hybrid population of Costa Rica (1968 samples). Three alleles, 126)7 (bp/copies of the repeat), 13118 and 136/9 were the most prevalent in all populations. Other alleles rarely reached frequencies of 10% or higher. Observed heterozygosities ranged between 0.351 and 0.829. Patterns of diversity fit well with both the geographic origin of the samples and the history of the populations screened. A statistical test suggests that single-step mutational events have been the main mechanism producing new alleles at this locus. Fixation indexes (R57) for this marker showed an effect of population subdivision on divergence only within the Asiatic group; they were insensitive at the level of major ethnic groups as well as within Africans and within EuropeansSe estudio el polimorfismo del microsatelite (AAAAI), del intron 1 del gene TP53 en 17 poblaciones de 3 grupos etnicos: europeos, asiaticos, y africanos subsaharianos, asi coma de la poblacion hibrida de Costa Rica (en total 1968 muestras). Tres aides, 12617 (pares de bases/ copias de la repetición), 131/8 y 136/9 fueron los mas frecuentes en todas las poblaciones, aunque se observaron otros alelos usualmente a frecuencias menores al 10%. Las heterocigosis observadas variaron de 0.351 a 0.829. La distribucion de la universidad parece concordar con el origen geográfico de las muestras y con la historia de las poblaciones estudiadas. Una prueba estadística indica que el evento mutacional que mas alelos nuevos produce en ese marcador es el de un solo paso (expansión o contracción de una cola copia de la repeticion). El indice de fijacion R„ mostro los efectos de la subdivision de poblaciones solo dentro del grupo de los asiaticos y mostro falta de sensibilidad cuando los grupos comparados eran de nivetes superiores de clasificacion (europeos, asiaticos, y africanos) o cuando la comparación se hizo entre los grupos mas antiguos (africanos y europeos).Universidad de costa Rica, Instituto de investigaciones en Salud.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Correlates of longitudinal leukocyte telomere length in the Costa Rican Longevity Study of Healthy Aging (CRELES): On the importance of DNA collection and storage procedures

The objective is to identify cofactors of leukocyte telomere length (LTL) in a Latin American population, specifically the association of LTL with 36 socio-demographic, early childhood, and health characteristics, as well as with DNA sample collection and storage procedures. The analysis is based on longitudinal information from a subsample of 1,261 individuals aged 60+ years at baseline from the Costa Rican Study of Longevity and Healthy Aging (CRELES): a nationally representative sample of elderly population. Random effects regression models for panel data were used to estimate the associations with LTL and its longitudinal changes. Sample collection procedures and DNA refrigerator storage time were strongly associated with LTL: telomeres are longer in blood collected in October-December, in DNA extracted from <1-year-old blood cells, and in DNA stored at 4°C for longer periods of time up to five years. The data confirmed that telomeres are shorter at older ages, as well as among males, and diabetic individuals, whereas telomeres are longer in the high-longevity Nicoya region. Most health, biomarkers, and early childhood indicators did not show significant associations with LTL. Longitudinal LTL variation over approximately two years was mainly associated with baseline LTL levels, as found in other studies. Our findings suggest that if there is unavoidable variability in season of sample collection and DNA storage time, these factors should be controlled for in all demographic and epidemiologic studies of LTL. However, due to unobserved components of measurement variation, statistical control may be inadequate as compared to standardization of data collection procedures.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Centro Centroamericano de Población (CCP)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biologí

Low endemicity and low pathogenicity of rotaviruses among rural children in Costa Rica

Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud. 1985Rotaviruses were prospectively studied in 51 rural Costa Rican children from birth to two years. Samples of feces were collected weekly over a 33-month period. Rotavirus was detected in 45 (1.04%) of 4,317 fecal specimens; 39 infections were documented (an incidence of 0.5 infection per child-year), only five of which were associated with diarrhea (a pathogenicity of 12.8%). Secretory antibody in fecal extracts, detected in six of 39 infections, was short lived and did not protect against reinfection. Serum antibody was present in 69.6% of two-year-old children, but was not detected in 18.8% with documented infections. On the other hand, serum antibody was present in six of 14 children in whom rotavirus was not detected, thus increasing the overall incidence to 0.6 infection per child-year. The combination of prolonged breast-feeding, exposure to a lower infecting dose (compared with urban children), and a higher standard of hygiene than expected may explain the low incidence and low pathogenicity of rotavirus among these rural children.Universidad de Costa Rica. Instituto de Investigaciones en Salud.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA