Riesgo de Desarrollo y Progresión de Cáncer Tiroideo Bien Diferenciado en pacientes con Variantes Genéticas del Gen de Tiroglobulina SER 734ala y ARG1980trp / Risk of Development and Progression of Well Differentiated Thyroid Cancer in patients with Genetic Variations of the Thyroglobulin SER734ala and ARG1980trp Genes

Introducción: Existen factores de riesgo que se asocian a desarrollo cáncer de tiroides diferenciado; la Tiroglobulina es una proteína ligada al tamaño tumoral, su rol dentro de las patologías oncológicas es controversial. El objetivo del estudio fue determinarsi las variaciones del gen de Tiroglobulina se asocian a la presencia de cáncer tiroideo. Métodos:Este estudio observacional de casos y controles se realizó con muestra no probabilística con muestras de patología de casos de cáncertiroideo diagnosticados en elHospital Oncológico Solón Espinosa Ayala de Quito. Se estableció un grupocontrol con voluntarios sanos. Se mide las variaciones SER734Ala y ARG1980 trp del gen de la Tiroglobulina. Se comparan las frecuencias con Chi cuadrado. Resultados:Un total de 51casos de cáncertiroideo y 50 controles. Variaciones en SER734Ala en el grupo de casos fueron homocigotos 24/51casos (53.3% (IC95% 38.8 -67.9%)en el grupo controlfueron24/50(53.3% (IC95% 38.8-67.9%)P=0.83. La variaciónheterocigotaARG1980 trp fueron en el grupo de casos 47/51(92.2%IC95% 84.3 -100%), en los controles 35/50(70% IC95% 56.6-83.4%)P=0.004. Conclusión:Se demostró que lasvariaciones del gen de laTiroglobulina pueden presentarse en pacientes con Cáncer Tiroideo en igual frecuencia que en voluntarios sanos

Introduction: There are risk factors associated with the development of differentiated thyroid cancer; Thyroglobulin is a protein linked to tumor size, its role in oncological pathologies is controversial. The objective of the study was to determine whether variations in the thyroglobulin gene are associated with the presence of thyroid cancer. Methods: This observational case-control study was conducted with a non-probabilistic sample with pathology samples from thyroid cancer cases diagnosed at the Solón Espinosa Ayala Oncological Hospital in Quito. A control group with healthy volunteers was established. The SER734Ala and ARG1980 trp variations of the Thyroglobulin gene are measured. The frequencies werecompared with Chi square. Results:A total of 51 thyroid cancer cases and 50 controls. Variations in SER734Ala in the group of cases were homozygous 24/51 cases (53.3% (CI95% 38.8 -67.9%) in the control group were 24/50 (53.3% (CI95% 38.8-67.9%) P = 0.83. Heterozygous ARG1980 trp were in the case group 47/51 (92.2% 95% CI 84.3 -100%), in the controls 35/50 (70% 95% CI 56.6-83.4%) P = 0.004. Conclusion:It was shown that variations of the Thyroglobulin gene couldoccur in patients with Thyroid Cancer in the same frequency as in healthy volunteers

Genetic diagnosis of hereditary hemochromatosis / 临床肝胆病杂志

Iron overload is not rarely seen in clinical practice, and hemochromatosis involving the liver is the most common type of iron overload. There is an extremely low incidence rate of the classic form of HFE hereditary hemochromatosis in the Asian population, which is different from the genetic background of the Caucasian population. European and American studies and international guidelines mainly focus on the HFE type, and there is low consistency between guidelines, with a lack of data from the Asian population. Therefore, with reference to the pathogenic genes of hereditary hemochromatosis and related data in China, this article discusses the genetic diagnosis of hereditary hemochromatosis, in order to provide a reference for the diagnosis and studies of hemochromatosis in the Chinese population.

Value of the methylation status of SDC2 and SFRP2 for colorectal cancer screening / 中华消化内镜杂志

Objective To explore the value of methylation of SDC2 and SFRP2 genes promoter in fecal DNA for colorectal cancer ( CRC) screening. Methods All stool samples were enrolled from Changhai Hospital of Naval Medical University, the Tenth People' s Hospital of Tongji University and the Seventh Medical Center of Chinese People's Liberation Army General Hospital. A total of 500 stool samples collected from March 2018 to December 2018 were allocated to CRC group ( 132 CRCs ) , adenoma group ( 38 advanced adenomas), healthy group (152 healthy individuals), interferential group (178 cases of benign colorectal disease or other non-colorectal tumors) and negative group (330 cases composed of healthy group and interferential group ) . The promoter methylation of fecal SDC2 and SFRP2 genes was detected by methylation-specific PCR (MSP) and compared with single gene methylation and the fecal immunochemical tests ( FIT) to evaluate its sensitivity and specificity. Results The stool sample analysis showed that the sensitivity of combined detection of SDC2 and SFRP2 in CRC group was 97. 73％ ( 129/132 ) , which was significantly higher than those of the single gene SDC2 test [ 70. 45％ ( 93/132) , P=0. 000] , single SFRP2 test [81. 82％ (108/132), P=0. 000] and FIT [69. 70％ (92/132), P=0. 000]. In adenoma group, the sensitivity of combined detection of SDC2 and SFRP2 was 57. 89％ (22/38), which was significantly higher than those of the single gene SDC2 test [ 15. 79％ ( 6/38 ) , P= 0. 000 ] and FIT [ 21. 05％ ( 8/38 ) , P=0. 021] , with no significant difference compared with that of SFRP2 test [ 47. 37％ ( 18/38) , P=0. 358] . In healthy group, the specificity of combined detection of SDC2 and SFRP2 was 98. 68％ (150/152), with no significant difference compared with those of single gene SDC2 test [ 100. 00％( 152/152) , P=0. 156] , single SFRP2 test [98. 68％ (150/152), P=1. 000] or FIT [95. 39％ (145/152), P=0. 091]. Specificities of combined detection of two genes in interferential and negative groups were 90. 45％ ( 161/178) and 94. 24％( 311/330) , which were significantly higher than 73. 03％( 130/178, P=0. 000) and 83. 33％( 275/330, P=0. 000) of FIT, respectively. Conclusion The combined detection test of methylation of SDC2 and SFRP2 is superior to single gene test, whose sensitivity of CRC and aggressive adenoma and specificity of distinguishing benign and malignant lesions are higher than FIT, which has potential application value.

Marcadores genéticos en hipertensión esencial / Genetic markers in essential hypertension

Essential hypertension (HTA) is a multifactorial disease and in Chile, its prevalence is 33.7 percent. There is a genetic predisposition to develop hypertension, whose magnitude is approximately 30 to 50 percent. At present, some factors are known to increase the risk for cardiovascular disease, but widely accepted biomarkers for screening are missing. The frst studies that looked for candidate genes have focused on the reninangiotensin - aldosterone, aducina, adrenoreceptors ß, G protein subunits, G protein signaling regulators, kinases associated with G proteins and Rho kinases. Studies of DNA sequencing, search for polymorphisms and variants through single nucleotide polymorphisms, have been used to seek partnerships with complex or multifactorial diseases, like HTA. Examples of these are: components of collagen proteins, genes related to cell myocardial proteins belonging to cytochrome P450 and growth factors, among others. It is still unlikely to count in a near future with a universal marker. Most probably, a series of markers that confer susceptibility to a specifc individual will have to be used in prevention programs or personalized therapy.

Aspectos imunogenéticos do parto pré-termo espontâneo / Immunogenetic aspects in spontaneous preterm birth

O parto pré-termo é uma das grandes intercorrências obstétricas, sendo a maior causa de morbidade e mortalidade perinatal. Dentre os diferentes fatores envolvidos no seu desencadeamento, a infecção intra-amniótica parece representar um papel central. As infecções desencadeiam resposta inflamatória nos tecidos materno e fetal, mediada pela produção de citocinas inflamatórias. As citocinas induzem a liberação de prostaglandinas, aumentando a contratilidade uterina, favorecendo a rotura das membranas fetais, a modificação e dilatação da cérvice e, finalmente, o parto pré-termo. A síntese de citocinas depende de controle genético. Diversos polimorfismos relacionados a genes humanos codificadores de citocinas são reconhecidos e associados a fenótipos de alta, média e baixa produção desses fatores. Assim sendo, a relação entre determinados genótipos e a ocorrência e/ou características de diferentes patologias tem sido investigada. Este tipo de abordagem pode contribuir para o conhecimento da patogenia, permitindo o reconhecimento de parâmetros preditivos e a definição de novas estratégias terapêuticas.

Preterm birth is a major obstetric incident and one of the main causes of perinatal mortality and morbidity. Among the different factors involved in its unleashing, intra-amniotic infection seems to play a central role. The infections unleash inflammatory response in both maternal and fetal tissues, mediated by the production of inflammatory cytokines. They also lead to liberation of prostaglandin, which increases myometrial contractility, favoring the rupture of fetal membrane, alteration and dilation of the cervix and, finally, preterm birth. The production of cytokines depends on genetic control. Many polymorphisms related to human genes that codify cytokines are recognized and associated with phenotypes of high, medium and low production of such factors. Thus, the relation between certain genotypes and the occurrence and/or characteristics of several pathologies has been the focus of investigations. This approach may contribute with a better understanding of the pathogenesis, allowing the identification of predictive parameters and the establishment of new intervention strategies.

Polimorfismos de genes de citocinas na pré-eclâmpsia / Polymorphisms of genes of cytokines in preeclampsia

A pré-eclâmpsia é uma forma de hipertensão exclusiva da gravidez, sendo uma das principais causas de morbimortalidade materna e perinatal em todo o mundo. Diversas evidências mostram que mecanismos imunológicos estão envolvidos em sua fisiopatologia. Neste contexto, a participação das citocinas parece exercer papel importante na ativação do processo inflamatório verificado na doença. Estes fatores estão presentes em todo o processo reprodutivo exercendo papéis tanto de ativação como de inibição de respostas celulares. A identificação dos genes que codificam a produção de diferentes citocinas e a possibilidade de ocorrência de polimorfismo destes genes, modulando eventualmente expressão clínica com padrões diferenciados, trouxe novas perspectivas para avaliar a participação destes mediadores na pré-eclâmpsia. Essa atualização descreve as principais citocinas relacionadas com a gestação e as pesquisas relacionadas aos polimorfismos de genes que codificam IL-10, IL-6, IFN-y, TGF-b e TNF-a na pré-eclâmpsia.

The pre-eclampsia is an exclusive form of hypertension in pregnancy, one of the major causes of fetal and maternal morbidity and mortality throughout the world. Several evidences show that immune mechanisms are involved in its pathogenesis. In this context, the participation of the cytokines seems to play an important role in the activation of the inflammatory process observed in the disease. These factors are present throughout the reproductive process playing a role in the activation as well as in the inhibition of cell answers. The genes identification that codifies the production of different cytokines and the possibility of occurrence of polymorphisms of these genes, modulating eventually clinical expression with differentiated patterns, brought new perspectives to evaluate the participation of these mediators in the preeclampsia. This updating describes the main cytokines related to the gestation and the researches related to the polymorphisms of genes that codify IL-10, IL-6, IFN-y, TGF-b e TNF-a in the pre-eclampsia.