Development of a small panel of SNPs to infer ancestry in Chileans that distinguishes Aymara and Mapuche components

BACKGROUND: Current South American populations trace their origins mainly to three continental ancestries, i.e. European, Amerindian and African. Individual variation in relative proportions of each of these ancestries may be confounded with socio-economic factors due to population stratification. Therefore, ancestry is a potential confounder variable that should be considered in epidemiologic studies and in public health plans. However, there are few studies that have assessed the ancestry of the current admixed Chilean population. This is partly due to the high cost of genome-scale technologies commonly used to estimate ancestry. In this study we have designed a small panel of SNPs to accurately assess ancestry in the largest sampling to date of the Chilean mestizo population (n = 3349) from eight cities. Our panel is also able to distinguish between the two main Amerindian components of Chileans: Aymara from the north and Mapuche from the south. RESULTS: A panel of 150 ancestry-informative markers (AIMs) of SNP type was selected to maximize ancestry informativeness and genome coverage. Of these, 147 were successfully genotyped by KASPar assays in 2843 samples, with an average missing rate of 0.012, and a 0.95 concordance with microarray data. The ancestries estimated with the panel of AIMs had relative high correlations (0.88 for European, 0.91 for Amerindian, 0.70 for Aymara, and 0.68 for Mapuche components) with those obtained with AXIOM LAT1 array. The country's average ancestry was 0.53 ± 0.14 European, 0.04 ± 0.04 African, and 0.42 ± 0.14 Amerindian, disaggregated into 0.18 ± 0.15 Aymara and 0.25 ± 0.13 Mapuche. However, Mapuche ancestry was highest in the south (40.03%) and Aymara in the north (35.61%) as expected from the historical location of these ethnic groups. We make our results available through an online app and demonstrate how it can be used to adjust for ancestry when testing association between incidence of a disease and nongenetic risk factors. CONCLUSIONS: We have conducted the most extensive sampling, across many different cities, of current Chilean population. Ancestry varied significantly by latitude and human development. The panel of AIMs is available to the community for estimating ancestry at low cost in Chileans and other populations with similar ancestry.

Factores asociados con el éxito de la terapia antitabaco en pacientes tratados con vareniclina: 10 años de experiencia en un programa multidisciplinario / Factors associated with success of a smoking cessation program

Background: Smoking cessation therapies include counseling, psychological management and pharmacological therapy. Varenicline is the most effective and safe medication available. Aim: To study risk factors for the failure of pharmacological smoking cessation therapy with varenicline. Patients and Methods: Retrospective analysis of 281 patients aged 45 ± 11 years (65% males) with a mean consumption of 31 ± 22 packs/year. They completed a smoking cessation program comprising psychological support and use of varenicline in a private clinic. Patients were followed with telephonic interviews during one year. A complete abstinence during one year was considered as a success of the program. Results: The success rate of the program was 53.4%. The factors associated with failure were a high tobacco dependence rate determined with the Fageström test (Odds ratio (OR) 2.47, 95% confidence intervals (CI) 1.16-5.26, p = 0.02). An instruction level of more than 12 years was associated with a lower failure rate (OR 0.38 95% CI 0.18-0.82). Conclusions: A high tobacco dependence rate and a lower education were associated with a higher failure rate of this smoking cessation program.

Muir-Torre Syndrome: case report and molecular characterization / Sindrome de Muir-Torre: relato de caso e caracterizacao molecular

CONTEXT: Muir-Torre syndrome is a rare autosomal dominant genodermatosis caused by mutations in the mismatch repair genes. It is characterized by the presence of sebaceous skin tumors and internal malignancies, affecting mainly the colon, rectum and urogenital tract. Awareness of this syndrome among physicians can lead to early diagnosis of these malignancies and a better prognosis. CASE REPORT: We report the case of a Chilean patient who, over the course of several years, had multiple skin lesions, endometrial cancer and colon cancer. The syndrome was diagnosed using molecular techniques such as microsatellite instability analysis, immunohistochemistry and DNA sequencing, which allowed us to find the causative mutation. CONCLUSION: Molecular diagnostics is a highly useful tool, since it allows clinicians to confirm the presence of mutations causing Muir-Torre syndrome. It is complementary to the analysis of the clinical data, such as dermatological presentation, presence of visceral malignancies and family history of colorectal tumors, and it provides important knowledge to help physicians and patients choose between treatment options. .

CONTEXTO: A síndrome de Muir-Torre é uma genodermatose autossômica dominante rara causada por mutações nos genes de reparo de incorreções. Caracteriza-se pela presença de tumores sebáceos da pele e doenças malignas internas, afetando principalmente cólon, reto e trato urogenital. A consciência desta síndrome pelos médicos pode levar ao diagnóstico precoce dessas doenças malignas e a um melhor prognóstico. RELATO DE CASO: Relatamos o caso de uma paciente chilena que, ao longo de vários anos, teve lesões cutâneas múltiplas, câncer de endométrio e câncer de cólon. A síndrome foi diagnosticada com técnicas moleculares, como a análise de instabilidade de microssatélites, imunoistoquímica e sequenciamento de DNA, o que nos permitiu encontrar a mutação causadora. CONCLUSÃO: Diagnóstico molecular é uma ferramenta muito útil, uma vez que permite que os clínicos confirmem a presença de mutações causadoras de síndrome de Muir-Torre. É complementar para a análise dos dados clínicos, tais como a apresentação dermatológica, a presença de doenças malignas viscerais e história familiar de tumores colorrectais, e fornece conhecimentos importantes para ajudar os médicos e os pacientes a escolher entre opções de tratamento. .

Resultados de un programa multidisciplinario para el control del hábito tabáquico / Results of a multidisciplinary program to quit smoking

Background: Therapies to quit smoking are based on counseling, psychological therapy (PT), nicotine replacement therapy, bupropion or varenidine. Aim: To report the results of a multidisciplinary program to quit smoking Material and Methods: Patients agedl8years or more, motivated to quit smoking were admitted in a program based in counseling and PT, with or without pharmacological therapy. They were assessed by telephone during one year offollow up. Patients with unstable psychiatric diseases were excluded. Results were considered as "successful" when patients maintained abstinence during the year offollow up. A logistic regression analysis was done to identify factors associated with treatment success. Results: Between 2005 and 2011, 198 patients aged 45 ± 11 years (56% males), who smoked 31.5 ± 20.6 packages/year, were treated. Ofthese, 155 (78%) were treated with varenidine, 26 (13%) with bupropion and 17 (9%>) did not receive pharmacological therapy. One hundred sixty eightpatients completed the year offollow up. In 82 (49%>), treatment was successful and was negatively associated with a history of depression (odds ratio = 4 (95% confidence intervals 1.23-38.33). The main side effeets associated to varenidine and bupropion were nausea in 37 and 23%o, sleep disorders in 20 and 19%o and headache in 12 and 0%>, respectively Conclusions: A multidisciplinary program to quit smoking achieved a 49%> of abstinence during a year offollow up.

Prevalence of the 35delG mutation in the GJB2 gene in two samples of non-syndromic deaf subjects from Chile

Hearing loss is the most common inherited sensorial deficiency in humans; about 1 in 1000 children suffer from severe or profound hearing loss at birth. Mutations in the GJB2 gene are the most common cause of prelingual, non-syndromic autosomal recessive deafness in many populations; the c.35delG mutation is the most common in Caucasian populations. The frequency of the c.35delG mutation was estimated in two samples of deaf patients from Santiago, Chile. Unrelated non-syndromic sensorioneural deaf patients were examined: Group 1 consisted of 47 unrelated individuals with neurosensory deafness referred to the Chilean Cochlear Implant Program; Group 2 included 66 school children with prelingual deafness attending special education institutions for deaf people. Individuals with profound to moderate isolated neurosensory hearing loss with unknown etiology were included. The presence of the c.35delG mutation was evaluated by the allele-specific polymerase chain reaction method (PCR), and in some cases it was confirmed by direct DNA sequencing of the coding region of the GJB2 gene. Deaf relatives were present in 20.3% of the cases. We found 19.5% (22/113) patients with the c.35delG mutation, 6 of them homozygous; these rates are similar to frequencies found in other Latin American countries.

Variantes de butirilcolinesterasa sérica en población de Santiago oriente / Serum butyrylcholinesterase variants in eastern Santiago

Succinylcholine causes prolonged apneas in a proportion if subjects that have genetical defect of butyrylcholinesterase, due to the presence of unusual alleles in the locus BCHE. To estimate allele frequences of 3 variants of serum butyrylcholinesterase, BCHE*U, BCHE*A and BCHE*F in an urban population of Santiago, Chile, different phenotypes for the locus BCHE were determined in 300 blood samples coming from patients of a private clinical laboratory. The population was formed by an admixture of Amerindian and European (mostly spanich) people. The frequency of BCHE*A was similar to the expected for this population, but BCHE*F frequency was greater than predicted. Eight subjects had a genotype BCHE AK. The higher frequency found for BCHE*F is probably due to the use of more precise detection techniques. Although the used method cannot distinguish BCHE UK from BCHE UU, the findings of individuals with BCHE AK, must lead to the suspicion that the frequency of the allel BCHE K is not negligible in Santiago

Distorsiones segregacionales de los sistemas ABO y Rh según el sexo en escolares del Area Norte de Santiago / Segregation distortions of ABO and Rh blood groups according to sex in school children of the Northern Area of Santiago

La hipótesis que los sistemas sanguíneos ABO y Rh y el sexo segreguen independientemente fue probada en una muestra de escolares, en la que algunas distorsiones del sistema ABO habían sido observadas. Se encontró heterogeneidad de la proporción de individuos O en las comparaciones pareadas entre grupos Rh y sexos, al estudiarlas por las pruebas, z, t y probabilidades exactas, pero no con la prueba de x2, los varones tuvieron una menor proporción de grupo O; los varones portadores del haplotipo cde presentaron una menor frecuencia de O, hecho que no se dio en las mujeres. El grupo RH8 (cDE/cde) tuvo una menor frecuencia de O que el resto y no se encontraron individuos BRH8

Patrones y valores de proteinas plasmaticas y eritrocitarias en escolares de 9 a 12 anos. / Patterns and values of plasma and erythrocyte proteins in school children from 9 to 12

Se estudian algunas proteinas plasmaticas y eritrocitarias mediante electroforesis.Se describen los fenotipos de haptoglobina (Hp), esterasa D (ESD) y fosfoglucomutasa (PGM1) y las cantidades absolutas y porcentuales de proteinas totales, albuminas, alfa 1, alfa 2, beta y gamma globulinas presentes en el plasma.Se encontro una variante de ESD. Las mujeres tienen valores superiores de gamma globulina plasmatica

Analisis del grupo sanguineo Rh en fratrias. Un nuevo sistema de histocompatibilidad en el hombre?. / Analysis of the Rh blood group in brothers. A new histocompatibility system in men?

Se examina el sistema sanguineo Rh en una muestra de ninos del Area Norte de Santiago.Los antisueros utilizados fueron: antiC, antic, antiD, antiE y antie. 73 parejas de hermanos quedaron incluidas en la muestra, los hermanos no tienen mas de tres anos de diferencia en edad que sus respectivos casos indices. Los casos indices presentaron frecuencias superiores de RH3(CDe/CDe) e inferiores de RH5(CDe/cDE) y RH6(CDe/cde) que las encontradas en la muestra de hermanos. De l7 parejas de hermanos donde los indices pertenecian al grupo RH3, solo un hermano tuvo ese mismo fenotipo,el resto se distribuyo en: RH5, RH6, RH7(cDE/cDE, 1) y Rh18 (cde/cde, 1). La probabilidad de produccion al azar de este resultado es P<0.00002. Para explicar estos resultados, postulamos que hay un sistema mayor de histocompatibilidad asociado al sistema Rh en el cromosoma 1 humano