Agregación familiar para cardiopatía isquémica

RESUMEN Fundamento: la cardiopatía isquémica es una entidad nosológica de origen multifactorial con predisposición genética y susceptible a cambios ambientales. Objetivo: determinar la existencia de agregación familiar para cardiopatía isquémica en pacientes atendidos en consulta de cardiología en el Hospital General Docente Vladimir Ilich Lenin de Holguín. Métodos: se realizó un estudio observacional, analítico de casos y controles (estudio de agregación familiar). La muestra quedó conformada por 60 nuevos pacientes con el diagnóstico de cardiopatía isquémica (casos) y por otros 60 pacientes sin diagnóstico de enfermedad coronaria (controles), pareadas en la razón 1:1. Se emplearon como variables: sexo, edad, antecedentes familiares de cardiopatía isquémica y factores de riesgo ambientales. Se utilizó el estadígrafo Chi cuadrado. Luego se calculó el Odds Ratio para conocer la magnitud de asociación mediante la razón de productos cruzados. Resultados: en el grupo casos existió una mayor frecuencia en el antecedente familiar para cardiopatía isquémica, fue más elevada para los familiares de primer grado con 31 familiares y un 41,3 %. La hiperlipidemia se presentó como el factor de riesgo de mayor frecuencia con 36,7 % en el grupo casos y 37,1 % en el grupo controles. Se determinó un riesgo aproximadamente 4 veces mayor de padecer cardiopatía isquémica en aquellos individuos con historia familiar positiva de primer grado, mientras que los pacientes con hiperlipidemia tienen 4,8 más riesgo de padecer cardiopatía isquémica. Conclusiones: existe agregación familiar para cardiopatía isquémica y se mostró un riesgo mayor de enfermar los pacientes con historia familiar positiva para la enfermedad, principalmente con familiares de primer grado y con hiperlipidemia.

ABSTRACT Background: ischemic heart disease is a nosological entity of multifactorial origin with genetic predisposition and susceptible to environmental changes. Objective: to determine the existence of familial aggregation for ischemic heart disease in patients seen in the cardiology clinic at the Vladimir Ilich Lenin General Teaching Hospital in Holguín. Methods: an analytical observational study of cases and controls (family aggregation study) was carried out. The sample was made up of 60 new patients with a diagnosis of ischemic heart disease (cases) and another 60 patients without a diagnosis of coronary heart disease (controls), paired in a 1:1 ratio. The following variables were used: sex, age, family history of ischemic heart disease and environmental risk factors: smoking, hyperlipidemia, high blood pressure and sedentary lifestyle. The Chi square statistician was used by the Mantel-Haenszel method. The odds ratio (OR) was then calculated to determine the magnitude of association through the ratio of cross products. Results: in the case group there was a higher frequency in the family history for ischemic heart disease, being higher for first degree relatives with 31 relatives and 41.3 %. Hyperlipidemia was the most frequent risk factor with 36.7 % in the case group and 37.1 % in the control group. An approximately 4-fold increased risk of suffering from ischemic heart disease was determined in those individuals with a positive first-degree family history, while patients with hyperlipidemia have a 4.8 times greater risk of suffering from ischemic heart disease. Conclusions: there is family aggregation for ischemic heart disease and a higher risk of getting sick was shown in patients with a positive family history for the disease, mainly with first-degree relatives and with hyperlipidemia.

Agregación familiar en individuos con hipertensión arterial esencial y factores de riesgo / Family Aggregation in Individuals with Essential Arterial Hypertension and Risk Factors

RESUMEN Fundamento: la hipertensión arterial es la elevación constante de las cifras de tensión arterial con un origen poligénico y mutifactorial. Es la hipertensión arterial una enfermedad de alta incidencia y prevalencia a nivel mundial. Objetivo: demostrar la agregación familiar para hipertensión arterial esencial y factores de riesgo en individuos afectados. Método: se realizó una investigación observacional, analítica, longitudinal y retrospectiva, de caso/ control a partir de la consulta de referencia para enfermedades crónicas no transmisibles en Banes, provincia Holguín durante el período octubre 2019 marzo 2020. El universo abarcó la totalidad de individuos diagnosticados y sus familias. Por muestreo aleatorio simple, se obtuvo la muestra de 91 casos. Se conformó el grupo control a razón de 3:1 que incluyó 273 individuos. Fueron cumplidos los requisitos bioéticos. Se aplicaron criterios de inclusión/exclusión. Fueron utilizados los estadígrafos: Chi cuadrado, Odd Ratio (OR), incluidos p e intervalo de confianza. Se operacionalizaron las variables: edad, sexo, grado de consanguinidad y factores de riesgo. Se obtuvo el árbol genealógico. Resultados: los grupos de edades 56-65 años y 66 años y más, resultaron los más afectados. Predominó el sexo masculino (53,9 %). Los familiares de primer y segundo grado de consanguinidad mostraron la mayor incidencia de la enfermedad. Se encontró asociación entre la enfermedad y el antecedente familiar de esta (X2=321,4), con un riesgo incrementado para los familiares de los casos respecto a los controles (OR=10,93). Los factores de riesgo predominantes fueron: tabaquismo (OR=2,18) y el antecedente familiar de enfermedad (OR=0,74). Se demostró la asociación de factores de riesgo con la enfermedad (X2=176,9). Conclusiones: la hipertensión arterial esencial es una enfermedad multifactorial, compleja y poligénica con agregación familiar demostrada.

ABSTRACT Background: arterial hypertension is the constant elevation of blood pressure figures with a polygenic and multifactorial origin. Hypertension is a disease of high incidence and prevalence worldwide. Objective: to demonstrate the familial aggregation for essential arterial hypertension and risk factors in affected individuals. Method: an observational, analytical, longitudinal and retrospective case / control investigation was carried out from the reference consultation for chronic non-communicable diseases in Banes, Holguín province during the period from October 2019 to March 2020. The universe covered all individuals diagnosed and their families. By simple random sampling, the sample of 91 cases was obtained. The control group was formed at a ratio of 3:1 which included 273 individuals. Bioethical requirements were met. Inclusion / exclusion criteria were applied. The following statistics were used: Chi square, Odd Ratio (OR), including p and confidence interval. The variables were operationalized: age, sex, degree of consanguinity, and risk factors. The genealogical tree was obtained. Results: the age groups 56-65 years and 66 years and over, were the most affected. The male sex predominated (53.9 %). First and second-degree relatives of consanguinity showed the highest incidence of the disease. An association was found between the disease and its family history (X2 = 321.4) with an increased risk for relatives of the cases compared to the controls (OR = 10.93). The predominant risk factors were: smoking (OR = 2.18) and family history of disease (OR = 0.74). The association of risk factors with the disease was demonstrated (X2 = 176.9). Conclusions: essential arterial hypertension is a multifactorial, complex and polygenic disease with demonstrated familial aggregation.

Agregación familiar y factores de riesgo de cáncer de mama en individuos afectados / Family Aggregation and Risk Factors for Breast Cancer in Affected Individuals

RESUMEN Fundamento el cáncer de mama es una enfermedad sistémica, multifactorial, polimorfa que se desarrolla en mujeres sin antecedentes familiares de la enfermedad. La posibilidad de herencia familiar se describe en 15-20 % de los casos. Objetivo: determinar la agregación familiar para cáncer de mama y los factores de riesgo asociados a este padecimiento. Método: se realizó un estudio analítico, retrospectivo, tipo caso y control, a partir de individuos que acudieron a la consulta municipal de riesgo genético, ubicada en el Policlínico Universitario César Fornet Frutos del municipio Banes, provincia Holguín en el período julio-diciembre de 2019 con el objetivo de comprobar la existencia o no de agregación familiar del cáncer de mama. Por muestreo aleatorio simple, se obtuvo la muestra conformada por 47 casos y 141 controles. Las variables operacionalizadas fueron: antecedentes personales y familiares de enfermedad oncológica, edad, menarquia, edad a la menopausia, ingestión de píldora anticonceptiva, edad de nacimiento de primer hijo, lactancia materna, ingestión de alcohol, hábito de fumar, historia familiar. Se aplicó un cuestionario diseñado a los fines del estudio. El cálculo de Chi cuadrado y Odds Ratio permitieron estimar asociación entre variables y la magnitud de asociación. Resultados: predominó el grupo de edad de 60-69 años. Los factores de riesgo hábito de fumar (OR=4,1), la ingestión de píldora anticonceptiva (OR=3,1), y el alcohol (OR=2,8) presentaron la mayor asociación a la enfermedad. Se propuso una estrategia de asesoramiento genético a partir de los resultados. Conclusiones: la confluencia de factores genéticos y ambientales, determina la agregación familiar del cáncer de mama.

ABSTRACT Foundation: breast cancer is a systemic, multifactorial, polymorphic disease that develops in women with no family history of the disease. The possibility of family inheritance is described in 15-20 % of cases. Objective: to determine the family aggregation for breast cancer and the risk factors associated with this disease. Method: an analytical, retrospective, case-control type study was carried out, from individuals who attended the municipal genetic risk consultation located at the César Fornet Frutos University Polyclinic, Banes municipality, Holguín province in the period July-December 2019 aimed at verifying the existence or not of family aggregation of breast cancer. By simple random sampling, the sample consisting of 47 cases and 141 controls was obtained. The sample, consisting of 47 cases and 141 controls, was obtained by simple random sampling. The variables were: personal and family history of oncological disease, age, menarche, age at menopause, contraceptive pill ingestion, first child age of birth, breastfeeding, alcohol intake, smoking, family history. A questionnaire designed for the purposes of the study was applied. The Chi square calculation and Odds Ratio allowed estimating association between variables and the magnitude of association. Results: the age group of 60-69 years prevailed. The risk factors for smoking (OR = 4.1), ingestion of the contraceptive pill (OR = 3.1), and alcohol (OR = 2.8) had the highest association with the disease. A genetic counseling strategy was proposed based on the results. Conclusions: confluence of genetic and environmental factors determines family aggregation of breast cancer.

Omic Approach in Non-smoker Female with Lung Squamous Cell Carcinoma Pinpoints to Germline Susceptibility and Personalized Medicine / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. MATERIALS AND METHODS: A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibswere subjected to a novel integrative “omic” approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger. A first-stepwhole-exome sequencing on tumor and normal tissue did not identify mutations in known driver genes. Building on the idea of a germline oligogenic origin of lung cancer, we performed whole-exome sequencing of DNA from patients' peripheral blood and their unaffected sibs. Finally, RNA-sequencing analysis in tumoral and matched non-tumoral tissues was carried out in order to investigate the clonal profile and the pathogenic role of the identified variants. RESULTS: Filtering for rare variants with Combined Annotation Dependent Depletion (CADD) > 25 and potentially damaging effect, we identified rare/private germline deleterious variants in 11 cancer-associated genes, none ofwhich, except one, sharedwith the healthy sib, pinpointing to a “private” oligogenic germline signature. Noteworthy, among these, two mutated genes, namely ACACA and DEPTOR, turned to be potential targets for therapy because related to known drivers, such as BRCA1 and EGFR. CONCLUSION: In the era of precision medicine, this report emphasizes the importance of an “omic” approach to uncover oligogenic germline signature underlying cancer development and to identify suitable therapeutic targets as well.

Análisis de la causalidad en el estudio genético de los trastornos neuropsiquiátricos: revisión narrativa / Causal analysis in the genetic study of neuropsychiatric disorders: Narrative review / Análise da causalidade no estudo genético dos transtornos neuropsiquiátricos: revisão narrativa

Los trastornos neuropsiquiátricos se caracterizan por formas complejas de transmisión genética. El conocimiento de los aspectos básicos de los diseños metodológicos más usados en la investigación sobre la genética de estos trastornos permite al clínico una búsqueda más eficaz de la literatura disponible, así como una mejor lectura crítica y aplicación práctica de los artículos sobre esta área del conocimiento. Esta revisión tiene como objetivo describir los diseños estadísticos-epidemiológicos más utilizados en este ámbito e ilustrar dicha descripción con algunos ejemplos. En concreto, se revisan aspectos metodológicos generales sobre los estudios de gemelos, los estudios de adopción, análisis de pedigríes, estudios de asociación (casos y controles) y análisis de ligamiento genético.

Neuropsychiatric disorders are characterized by complex forms of genetic transmission. Knowledge of the basic aspects of the most commonly used methodological designs used in research on the genetics of these disorders allows the clinician to perform a more effective search of the literature available as well as a better critical reading and practical application of the articles in this field of knowledge. The objectives of this review are to describe the statistical-epidemiological designs that are most commonly used in this field and to illustrate this description with several examples. Specifically, we review the general methodological aspects of twin studies, adoption studies, pedigree analysis, association studies (case-control), and genetic linkage analysis.

Os transtornos neuropsiquiátricos se caracterizam por formas complexas de transmissão genética. O conhecimento dos aspectos básicos dos desenhos metodológicos mais usados na investigação sobre a genética destes transtornos permite ao clínico uma busca mais eficaz da literatura disponível, assim como uma melhora na leitura crítica e na aplicação prática dos artigos sobre esta área do conhecimento. Esta revisão tem como objetivo descrever os desenhos estatísticos-epidemiológicos mais utilizados neste âmbito e ilustrar dita descrição com alguns exemplos. Em concreto, se revisam aspectos metodológicos gerais sobre os estudos de gêmeos, os estudos de adoção, análise de pedigrees, estudos de associação (casos e controles) e análise de ligamento genético.

Refinando o diagnóstico de Transtorno de Oposição e Desafio na infância e adolescência: validação e caracterização da dimensão irritável / Refining Oppositional Defiant Disorder diagnosis in children and adolescents: validation and characterization of the irritable dimension

O Transtorno de Oposição e Desafio (TOD) é definido por um padrão recorrente de comportamento desafiante, desobediente e hostil com início na infância e adolescência e caracteriza-se por uma alta taxa de comorbidades. Estudos longitudinais apontam o TOD na infância como um dos principais preditores de psicopatologia na idade adulta. Uma possível explicação para a grande heterogeneidade de comorbidades e trajetórias longitudinais é de que o diagnóstico de TOD abrange distintas dimensões de sintomas, cada qual com seu desfecho. O primeiro objetivo desta tese foi a validação das distintas dimensões do TOD em uma amostra comunitária Brasileira composta de 2512 sujeitos. Através de análise fatorial confirmatória, demonstramos que o modelo que melhor representa a heterogeneidade do TOD é composto por três dimensões: a dimensão "argumentative/defiant" que está associada com transtorno de déficit de atenção/hiperatividade (TDAH); a dimensão "vindictiveness" que possui associação com transtorno de conduta (TC); e a dimensão "angry/irritable mood" onde predominam as associações com transtornos depressivos e de ansiedade. O objetivo seguinte foi investigar o papel da dimensão irritável na classificação nosológica dos transtornos mentais na infância e adolescência. A apresentação da irritabilidade é um aspecto crucial: irritabilidade crônica caracterizada por baixa tolerância à frustração e frequentes explosões de raiva, que é distinta da apresentação episódica, associada ao diagnóstico Transtorno de Humor Bipolar (TB). "Severe mood dysregulation", "disruptive mood dysregulation disorder", ou dimensão irritável do TOD são formas distintas de classificar o fenótipo de irritabilidade crônica. Entretanto, independente da classificação utilizada, a alta taxa de comorbidades é invariavelmente o denominador comum em estudos sobre irritabilidade. Neste sentido, examinamos o impacto da irritabilidade como uma dimensão subjacente a vários transtornos. Para tanto, avaliamos o...

The Oppositional Defiant Disorder (ODD) is defined as a pattern of disobedient, hostile and defiant behavior beginning in childhood or adolescence and often accompanied by a wide range of comorbidities. Longitudinal studies support ODD as a predictor of psychopathology in adulthood. A potential explanation for such heterogeneity of comorbidities and longitudinal trajectories is that ODD diagnosis encompasses distinct clusters of symptoms, each with its outcome. The first aim of this work was the validation of ODD dimensions in a Brazilian community sample of 2512 subjects. Confirmatory factorial analysis showed that the best model for ODD comprised three dimensions: an "argumentative/defiant" dimension, which associates with attention deficit/hyperactivity disorder (ADHD); a "vindictiveness" dimension, which associates with conduct disorder (CD); and an "angry/irritable" dimension where emotional disorders such as depression and anxiety are the most common associations. The next step was the investigation of the role of the irritable dimension of oppositionality in diagnostic classifications of childhood mental disorders. The pattern of irritability is a crucial point: its chronic presentation as easy annoyance and frequent temper outbursts should be differentiated from the episodic course of irritability associated with the specific diagnosis of Bipolar Disorder (BD). "Severe mood dysregulation", "disruptive mood dysregulation disorder", and the irritable dimension of oppositionality are different ways to classify the chronic irritability phenotype. However, regardless of the classification, the high rate of comorbidities is invariably the common denominator in studies of irritability. Therefore, we examined the impact of irritability as a dimension cutting across multiple settings: individuals without any diagnosis, subjects with ADHD, and also those with emotional disorders. For that we used two samples, one from Brazil, with 2.512 subjects, and one...

Asociación y efectos de interacción en los genes AGT , AGTR1 , ACE , ADRB2 , DRD1 , ADD1, ADD2, ATP2B1, TBXA2R y PTGS2 sobre la hipertensión en la población antioqueña / Association and interaction of AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R and PTGS2 genes on the risk of hypertension in Antioquian population

Introducción. La hipertensión arterial es una enfermedad multifactorial influenciada por componentes genéticos y ambientales, cuya prevalencia varía entre grupos étnicos. Se han llevado a cabo numerosos estudios en genes de sistemas reguladores de la presión arterial, como el sistema renina-angiotensinaaldosterona, el sistema nervioso simpático, los factores endoteliales, y el balance de sodio, mostrando resultados incongruentes entre poblaciones. Objetivos. Evaluar el efecto de variantes en los genes AGT , AGTR1 , ACE , ADRB2 , DRD1 , ADD1 , ADD2 , ATP2B1 , TBXA2R y PTGS2 y del componente ancestral individual, sobre la hipertensión arterial y las cifras de presión arterial en una muestra de población antioqueña. Materiales y métodos. Se genotipificaron 107 casos y 253 controles para 12 variantes en los genes AGT , AGTR1 , ACE , ADRB2 , DRD1 , ADD1 , ADD2 , ATP2B1 , TBXA2R y PTGS2 , y para 20 marcadores informativos de ascendencia. Se evaluó la asociación de los polimorfismos y sus interacciones, y de la composición genética ancestral con hipertensión y cifras de presión arterial. Resultados. Los genes ADD2 , rs4852706 (OR=3,0; p=0,023); DRD1 , rs686 (OR=0,38; p=0,012) y ADRB2 , rs1042718 (OR=10,0; p=0,008); y combinaciones genotípicas de DRD1 con AGTR1 ; de AGT con ADD1 ; y de ADD1 con ATP2B1 y PTGS2 , se asociaron con hipertensión arterial. El componente ancestral amerindio se asoció con disminución en la presión arterial diastólica. Conclusiones. Variantes en los genes ADD2 , DRD1 , ADRB2 , AGTR1 , AGT , ADD1 , ATP2B1 y PTGS2 , individualmente o en su interacción, se encuentran asociadas con hipertensión. El componente ancestral amerindio tiene un efecto sobre las cifras de presión arterial.

Introduction: Hypertension is a multifactorial disease influenced by genetic and environmental components, with its prevalence varying across ethnic groups. Manifold studies on blood pressure regulatory system genes have been carried out -such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, endothelial factor, and sodium balance-, but the results yielded were inconsistent among populations. Objectives: To evaluate the effect of both variants in genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R PTGS2, and the result of the individual ancestry component on hypertension and blood pressure levels among population in Antioquia. Methods and materials: 107 cases and 253 controls were genotyped for 12 variants on genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2, and for 20 ancestry informative markers. The association of polymorphisms and their interactions, and the association of ancestral genetic composition with hypertension and blood pressure levels were examined. Results: Genes ADD2, rs4852706 (OR=3.0; p=0.023); DRD1, rs686 (OR=0.38; p=0.012) and ADRB2, rs1042718 (OR=10.0; p=0.008); as well as genotypic combinations of DRD1 and AGTR1; AGT and ADD1; and ADD1 to ATP2B1 and PTGS2 were associated to hypertension. The Amerindian ancestry component was associated to some decrease in diastolic blood pressure. Conclusion: Variants on genes ADD2, DRD1, ADRB2, AGTR1, AGT, ADD1, ATP2B1 and PTGS2 individually or interacting, are associated to hypertension. The Amerindian ancestry component has an effect on blood pressure.

Estenosis espinal lumbar degenerativa / Degenerative spinal lumbar stenosis

Fundamento: el aumento progresivo de la esperanza de vida viene acompañado de una mayor incidencia de las enfermedades degenerativas del raquis como la estenosis espinal. Objetivo: actualizar y sistematizar los conocimientos sobre la estenosis espinal degenerativa del canal espinal lumbar. Método: se realizó una revisión de la literatura de los último cinco años. Se insistió en la clasificación, patogenia, diagnóstico y tratamiento. Desarrollo: la estenosis espinal degenerativa del canal lumbar es un desorden multifactorial caracterizado por un estrechamiento del canal vertebral, del receso lateral o de los agujeros de conjunción secundaria a hipertrofia degenerativa y progresiva de cualquiera de las estructuras óseas, cartilaginosas o ligamentosas que culmina en una compresión neurológica y vascular. La claudicación neurogéna es de los síntomas más característicos. El diagnóstico se basa en las mediciones realizadas en las imágenes de tomografía axial computarizada y en la resonancia nuclear magnética. Las opciones terapéuticas incluyen el tratamiento conservador y el quirúrgico, con las técnicas descompresivas convencionales y las de mínima invasión, preferidas en la actualidad. Conclusiones: la estenosis espinal degenerativa es una enfermedad multifactorial. El diagnóstico se fundamenta en la sospecha clínica confirmada en los estudios imagenológicos. Para la elección del tratamiento deben tenerse en cuenta factores relacionados con el paciente, con las características de la estenosis y con la disponibilidad de la tecnología. El objetivo de la cirugía se encaminará a descomprimir las estructuras neurovasculares y respetar la estabilidad del raquis para disminuir la morbilidad posoperatoria.

Background: the progressive increase of life expectancy came along with a greater incidence of degenerative diseases of the rachis like spinal stenosis. Objective: to systematize and bring the knowledge about degenerative spinal stenosis of the spinal lumbar channel up to date. Method: a review of the literature from the last five years was made, making emphasis in the classification, pathogeny, diagnosis, and treatment. Development: degenerative spinal stenosis of the lumbar channel is a multifactorial disorder characterized by a narrowing of the vertebral channel, of the lateral recess, or of the secondary intervertebral foramina, conditions commonly observed in degenerative and progressive hypertrophy of any of the cartilaginous, ligamentous, or osseous structures that ends in a neurologic or vascular squeeze. Neurogenic claudication is one of the most characteristic symptoms. The diagnosis is based on measuring made through the images in the computerized axial tomography and in the nuclear magnetic resonance. The therapeutic options include the conservative treatment and the surgical treatment, with conventional decompressing techniques and the techniques of minimal invasion that are the most used nowadays. Conclusions: degenerative spinal stenosis is a multifactorial disease. The diagnosis is based on the clinical suspicion confirmed through imagenology studies. Some factors related to the patient, to the characteristics of the stenosis, and to the availability of the technology should be taken into consideration for choosing the treatment. The objective of the surgery will be aimed at decompressing the neurovascular structures and keeping the stability of the rachis in order to reduce the postoperative morbidity.

Association of transforming growth factor-β1 gene +869T/C polymorphism with autoimmune thyroid disease / 中国地方病学杂志

Objective To clarify whether the +869T/C polymorphism in the transforming growth factor-β1 (TGF-β1) gene is associated with TGF-β1 expression,and involved in the severity of Graves disease(GD) and Hashimoto's thyroiditis(HT).Methods The TGF-β1+869T/C polymorphism was genotyped by using PCR-sequence specific primers(PCR-SSP) in genomic DNA samples in blood from 158 patients with HT who developed hypothyroidism before they were 45 years old (severe HT) and 125 untreated,euthyroid patients with HT who were older than 45(mild HT).Using the same method,129 euthyroid patients with GD who had been under treatment and were still positive for anti-thyrotropin receptor antibodies (intractable GD) and 130 euthyroid patients with GD in remission and 144 healthy controls were examined.Results It had no difference between GD,HT groups and control group (x2 =1.488,0.439; 0.626,0.005; all P ＞ 0.05 ).The frequency of the TT genotype and the T allele were higher in group with severe HT[34.81％(55/158),58.86％( 186/316)] than in those with mild HT[ 17.60％ (22/125),43.60％ (109/250); x2 =14.040,13.026,all P ＜ 0.05].In contrast,the frequency of the CC genotype was higher in group with intractable GD[ (21.03％(31/129),51.16％(132/258)] than in group with GD in remission[ 13.85％ (18/130),40.38％( 105/260); x2 =12.225,6.061,all P ＜ 0.05 ].TGF-β1 +869 T/C genotype had the correlation with severe groups of HT and GD.C allele would increase in severity of GD(OR =1.546,95％ CI =0.192 - 2.190),and T allele would increase in severity of HT(OR =1.851,95％ CI =1.323 - 2.589).Conclusion The +869T/C polymorphism in the TGF-β1 gene is associated with the severity and intractability of autoimmune thyroid disease.

Investigation of risk factors in the liver cancer of Wuwei city / 肿瘤研究与临床

Objective To investigate the widespread of the liver cancer risk factors in Wuwei city,where low-incidence for liver cancer and offer the cause clue to first-level prevention. Methods Investigate the risk factor and family history of the Wuwei city resident who wlth liver cancer by using case-control study.Estimate the liver cancer heredity mode with the method of Penrose and simple segregation analysis,calculate the degree of heritability with the metllod of Falconer,s regression.Detect the content of the resulting and promoting cancer fungi,volatility N-second nitroso compound in the meal,nitrate and nitrite in the drinking water and the vitamin C in the health adults'serum by means of culturing appraisement,experiment examination etc.Results The risk factom of liver cancer in the Wuwei city were history of viral 'hepatitis type B,kinsfolk tumor,the eating salting or mildewed foods,cirrhosis,drinking surface water,well water,or wine.By using segregation analysis and estimation of heredity mode show that the morbidity of liver cancer discrepancy to the monogenic inheritance mode,maybe the polygenic inheritance mode in Wuwei city.The h~2 of index case first degree relative was 58.74%.Picking out 8 kinds of nitrosamine,14 kinds of resulting and promoting cancer fungi from resident meal.The content of nitrate and nitrite was (38.97±3.14) mg/L,(0.086±0.043) mg/L respectively in shallow well water,the vitamin C in the health adults'serum in summer was(5.74±2.79)mg/L.Conclusion It can be seen that the history of viral hepatitis type B,kinsfolk tumor,eating salting or mildewed foods,cirrhosis,addicted to drink;higher content of nitrate and nitrite in the drinking water and strong carcinogens such as volatility N-nitroso compound in the meal,and also lackingprotection factors such as vitamin C are the risk factors of the Wuwei city resident who with liver cancer,Theinherit susceptivity is the internal environment of resulting cancer change.

Novel strategies to identify relevant molecular signatures for complex human diseases based on data of identical-by-decent profiles and genomic context / 北京大学学报(医学版)

Objective: To develop novel strategies to identify relevant molecular signatures for complex human diseases based on data of identical-by-decent profiles and genomic context.Methods: In the proposed strategies, we define four relevancy criteria for mapping SNP-phenotype relationships-point-wise IBD mean difference, averaged IBD difference for window, Z curve and averaged slope for window.Results: Application of these criteria and permutation test to 100 simulated replicates for two hypothetical American populations to extract the relevant SNPs for alcoholism based on sib-pair IBD profiles of pedigrees demonstrates that the proposed strategies have successfully identified most of the simulated true loci.Conclusion: The data mining practice implies that IBD statistic and genomic context could be used as the informatics for locating the underlying genes for complex human diseases. Compared with the classical Haseman-Elston sib-pair regression method, the proposed strategies are more efficient for large-scale genomic mining.

Familial Occurrence of Moyamoya Disease: Case Report

There is extensive evidence that moyamoya disease has a tendency for multifactorial inheritance, although the pathogenesis of moyamoya disease is not clear. The authors report a case of familial moyamoya disease involving a 51-year-old female and her 24-year-old daughter, both of whom initially presented, within a 1-year period, withintracerebral hemorrhage and intraventricular hemorrhage. Cerebral angiography showed typical features of moyamoya disease in both patients, but the cause of the pathology remains obscure. The pertinent literature is reviewed.

A Case of Atrial Septal Defect in Identical Twins

Atrial septal defect is one of the most common congenital heart diseases in adult, of which absolute causes is not confirmed, but explained by multifactorial inheritance. In Korea, there has been no case report of atrial septal defect in identical twins in spite of some reports of atrial septal defect in relatives and twins in other countries. We present a first case of atrial septal defect in identical twins whose mother had no infection or medication history during pregnancy.