Factores de riesgo socio-demográficos del síndrome cardiopulmonar por hantavirus / Sociodemographic risk factors of hantavirus cardiopulmonary syndrome

Resumen Introducción: El síndrome cardiopulmonar por hantavirus (SCPH) es causado en Chile y en el sur de Argentina por el Andes hantavirus (ANDV), el que es endémico en esta zona. La enfermedad causada por ANDV produce un aumento de permeabilidad vascular y filtración de plasma con una alta tasa de letalidad (35%), debido principalmente a insuficiencia respiratoria por edema pulmonar y al desarrollo en los casos graves de compromiso miocárdico, hipoperfusión y shock. Aunque se sabe que los factores socio-demográficos del hospedero pueden influir en el curso y el resultado de la enfermedad, estos no se han caracterizado previamente en la población chilena. Objetivo: Evaluar la relación entre los factores socio-demográficos y la gravedad del SCPH. Pacientes y Métodos: Período de análisis 2004-20013, pacientes atendidos en ocho centros colaboradores, diagnóstico etiológico serológico o por biología molecular, se comparan SCPH leve y grave. Se analizaron 139 pacientes chilenos, 64 (46%) con enfermedad grave, entre los cuales 12 murieron (19%). Resultados: La etnia europea tuvo un riesgo 5,1 veces mayor de desarrollar un SCPH grave que la etnia amerindia, gravedad mayor que también se asoció a una residencia urbana. Conclusiones: Se observó una asociación estadísticamente significativa entre etnia, lugar de residencia y evolución de SCPH. Se discuten hipótesis que expliquen estos hallazgos.

Background: Hantavirus cardiopulmonary syndrome (HCPS) is caused by new world hantaviruses, among which Andes hantavirus (ANDV) is endemic to Chile and Southern Argentina. The disease caused by ANDV produces plasma leakage leading to enhanced vascular permeability and has a high case fatality rate (35%), mainly due to respiratory failure, pulmonary edema and myocardial dysfunction, hypoperfusion and shock. Host sociodemographic and genetic factors might influence the course and outcome of the disease. Yet, they have not been thoroughly characterized. Aim: To evaluate sociodemographic factors as risk factors in severity of HCPS. Patients and Methods: Study period: 2004-20013, attending in eight collaborative centers, etiological diagnosis was performed by serology or molecular biology, mild and severe HCPS were compared.139 Chilean patients were analyzed, 64 (46%) with severe disease among which 12 (19 %) died. Results: European ethnicity had 5,1 times higher risk than Amerindian ethnic group to develop a severe HCPS, greater seriousness that was also associated with an urban residence. Conclusion: It was observed that ethnicity and type of residence were significant risk factors for HCPS severity. Hypotheses explaining these findings are discussed.

Combinación de genotipos DRD4 y DAT1 constituye importante factor de riesgo en miembros de familias de Santiago de Chile con déficit atencional / Combination of DRD4 and DAT1 genotypes is an important risk factor for attention déficit disorder with hyperactivity families living in Santiago, Chile

Background: Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness, and/or inattentiveness. Aún: To search forpossible associations between dopamine receptor D4 (DRD4) and dopamine transponer 1 (DATl) polymorphisms and ADHD in Chilean families. Material and methods: We extended a previous family-based discordant sib pair analysis that included 26 cases diagnosed according to DSM-IV entena and 25 controls (healthy siblings of cases), adding 14 cases and 11 controls. Results: Both loci, individually classified as homozygotes or heterozygotes for the DRD4 7-repeat and DATl 10-repeat alleles, did not exhibit genotype frequency differences between affected children and their healthy siblings. However, the simultaneous presence of both DRD4 7-repeat heterozygosity and DATl 10 allele homozygosity was significantly higher (22.5 percent) in cases (40), compared with (2.8 percent) unaffected siblings (36), with an odds-ratio of 10.16. Conclusions: The genotype combination DRD4/7 heterozygotes and DAT1/10 homozygotes is a high risk factors in Chilean families for ADHD. Increased density of dopamine transporters in ADHD brains, along with abundance of 7-repeat D4 receptors in prefrontal cortex, which is impaired in ADHD patients, make the observed gene-gene interaction worthy of studies to understand the functional basis ofADHD.

Susceptibilidad genética a hantavirus Andes: Asociación entre la expresión clínica de la infección y alelos del sistema HLA en pacientes chilenos / Genetic susceptibility to Andes Hantavirus: Association between severity of disease and HLA alíeles in Chilean patients

En Chile, la infección por hantavirus Andes (ANDV) tiene una expresión clínica variable, reconociéndose diversos grados de severidad. El presente estudio se realizó con el objeto de analizar la posible asociación entre la constitución genética de pacientes chilenos para el sistema HLA y la expresión clínica de la infección por ANDV. Se analizaron los alelos HLA A, B, DRB1 y DQB1, en dos grupos de pacientes con infección por ANDV: 41 pacientes con evolución clínica leve (sin insuficiencia respiratoria severa y sin requerimientos de ventilación mecánica) y 46 pacientes con evolución clínica grave (con insuficiencia respiratoria grave y/o shock). La determinación molecular del sistema HLA se realizó mediante SSP-PCR. El alelo HLA DRB1 * 15, se encontró en una frecuencia significativamente más alta en los pacientes leves (p = 0,007). Por lo tanto, el alelo DRB 1*15 se asociaría al curso clínico leve de la enfermedad. El alelo HLA-B*08, se encontró en una frecuencia mayor en los pacientes graves, la diferencia alcanzó una significación estadística marginal (p = 0,06). Así, el alelo HLA-B*08, podría estar asociado al curso clínico grave de síndrome cardiopulmonar ocasionado por hantavirus Andes.

Andes hantavirus (ANDV) infection in Chile has a variable clinical expression, and infected individuals may present with different grades of disease severity. This study aimed to determine if clinical expression of ANDV infection in Chilean patients is associated with the HLA system. HLA alíeles A, B, DRB1 and DQB1, were studied in two groups of patients with confirmed ANDV infection: 41 patients with a mild disease course (without respiratory failure and cardiovascular shock) and 46 patients with a severe disease course (with respiratory failure and shock). Molecular typing of HLA system was performed by SSP-PCR. The HLA-DRB 1*15 alíele, was significantly more common in the group of patients with mild disease (p = 0,007) and thus for possibly associated with a protective effect against ANDV infection. Conversely, HLA-B*08 was more common in patients with severe disease (p = 0,06). Although the association was marginally significant, alíele HLA-B*08 may be linked to an increased susceptibility to the severe clinical course of HCPS by ANDV.

Caracterización molecular de alelos ABO*O del locus de grupo sanguíneo ABO en tres poblaciones chilenas / Molecular Characterization of ABO*O Alleles at the ABO Group Locus in Three Chilean Populations

Background: Among the allelic variants of blood groups, the molecular characterization of ABO blood group has clinical and anthropological importance. Aim: To perform a characterization of the molecular variants of the allele ABO*O of the ABO blood group. Material and methods: Eighty four subjects of Aymara origin, living in Northern Chile, 75 individuals of Huilliche origin, living in Southern Chile and 82 subjects living in Santiago (Central Chile), were studied. All individuals were of group O, homozygotes for G261- deletion, that defines O1 alleles. Mutations G188A, G261-, G542A, T646A and C771T, described for alleles O1, O1variant and G542A were determined by PCR-RFLP (polymerase chain reaction-restriction fragment lenght polymorphism). Results: Allele O1variant has frequencies of 0.65, 0.81 and 0.6 in Aymara, Huilliche and Santiago subjects, respectively. The figures for allele O1 are 0.35, 0.19 and 0.4, respectively and those for the allele with G542A mutation are 0.119, 0.113 and 0.079, respectively. Conclusions: These results are concordant with the reported higher frequency of allele O1variant in South American aboriginal populations. The frequencies of G542A allele in these Chilean individuals are lower than those described for Amazon aborigines.

Caracterización genético molecular de habitantes de Caleta Paposo, último reducto Chango en Chile / Molecular and genetic characterization of Changos descendants living in Paposo Cove

Background: There are geographic and ethno historic evidences that relate Paposo cove, located 150 km south of the city of Antofagasta, with old fishermen-collector populations known as Changos, that lived in that zone in the XVII and XVIII centuries. Aim: To perform a genetic and molecular characterization of current Paposo inhabitants, through mitochondrial DNA polymorphism analysis and molecular analysis of classical ABO and Duffy blood groups. Material and methods: Forty unrelated individuals were studied. The presence of restriction polymorphisms that define A, B, C, and D Amerindian founder mitochondrial haplogroups was studied and molecular determination of classical blood groups were done by PCR. Results: One individual had A haplogroup (2.5 percent), 19 had B haplogroup (47.5 percent), six had C haplogroup (15 percent) and 11 had D haplogroup (27.5 percent). Three subjects (7.5 percent) did not have any of these haplogroups. Among ABO blood groups, the frequency of O101 allele was 0.39, that of allele O201 was 0.53 and that of A allele was 0.08. Duffy blood group frequencies were 0.58 for FY*A and 0.42 for FY*B. FY null allele was not found. Conclusions: The frequency distribution of Amerindian mitochondrial haplogroups in Paposo inhabitants suggest that these individuals are related with Aymara and Atacameño Amerindians that can be considered culturally and geographically close populations. This proposal is supported by the results of the molecular determination of classical blood groups. Our findings in Paposo cove may represent the distribution of these markers in Chango Indians, of whom there is limited physical evidence and that became extinct near 1890 (Rev Méd Chile 2004; 132: 663-72).

Composición genética de la población chilena: los atacameños de la comuna de San Pedro de Atacama / Genetic composition of chilean population: the atacameños from San Pedro de Atacama

This work describes the genetic composition of atacameños from San Pedro de Atacama. The results show that a) the contribution of non-indigenous genes is relatively low, in relation to the spanish inmigration period. b) the Hardy-Weinberg genetics disequilibrium for MNSs system should have biological implications. c) the variant for esterasa D enzyme may be the same found in other chilean populations

Composición genética de la población chilena: los yamanas de Ukika / Genetic composition of chilean population: the yamanas from Ukika

The genetic composition of a group of 24 Yamana indians that survive in Puerto Williams, navarino Island, Chile (parallel 55 south of Tierra del Fuego), was studied. Results showed that these indians have a different genetic composition than Pehuenche indians, specially for HLA system and sterase D. This fact validates the hypothesis based on archeological and antropological evidence, about the paleoindian origin of Yamanas