Abordagem da hiperplasia adrenal congênita pela deficiência da enzima 21-hidroxilase em crianças e adolescentes: revisão / Management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in children and adolescents: review

Objetivo: Descrever o diagnóstico e manejo clínico da deficiência da 21-hidroxilase (D-21OH), no contexto atual de inclusão da doença nos programas de triagem neonatal, bem como características genéticas, fisiopatológicas e manifestações na infância e adolescência. Fonte de Dados: Revisão integrativa realizada nas bases de dados MEDLINE (PubMed), LILACS (BVS), Scopus, Web of Science nos últimos vinte anos, em língua inglesa e portuguesa; população-alvo: crianças da primeira infância à adolescência; com o uso dos termos "triagem neonatal", "hiperplasia adrenal congênita", "deficiência da 21-hidroxilase", "glucocorticoide" e "polimorfismos do gene NR3C1". Síntese de Dados: A hiperplasia adrenal congênita (HAC) constitui um grupo de doenças caracterizadas por deficiências enzimáticas na esteroidogênese do córtex adrenal. A D-21OH é responsável por 95% dos casos e, se não tratada precocemente, pode levar ao óbito no período neonatal em sua forma clássica. A triagem neonatal para a HAC consiste na dosagem do precursor 17-hidroxiprogesterona (17OHP) no sangue de recém-nascidos, permitindo rápida confirmação diagnóstica e instituição da terapêutica. A implantação da triagem neonatal constitui um avanço, mas o controle dos pacientes pediátricos com D-21OH é complexo e deve ser sempre individualizado. Conclusão: A instituição dos programas de triagem neonatal para HAC tem trazido benefícios para o prognóstico das crianças com D-21OH. Seu manejo é multiprofissional, individualizado e ainda um desafio mesmo para o especialista. Ampla divulgação do conhecimento sobre a doença é desejável para permitir melhor condução dessas crianças, especialmente de meninas com a doença que apresentam genitália atípica.

Objective: To describe the diagnosis and clinical management of 21-hydroxylase deficiency (21OH-D), in the current context of including the disease in neonatal screening programs, as well as genetic, pathophysiological characteristics, and manifestations in childhood and adolescence. Data Source: Integrative review performed in MEDLINE (PubMed), LILACS (BVS), Scopus, Web of Science databases in the last twenty years, in English and Portuguese; target population: children from early childhood to adolescence; with the use of the terms "neonatal screening"; "congenital adrenal hyperplasia"; "21-hydroxylase deficiency"; "glucocorticoid"; "polymorphisms of the NR3C1 gene". Data Synthesis: Congenital adrenal hyperplasia (CAH) is a group of diseases characterized by enzyme deficiencies in adrenal cortex steroidogenesis. 21OH-D is responsible for 95% of cases and, if not treated early, can lead to death in the neonatal period in its classic form. Neonatal screening for CAH consists of measuring the precursor 17-hydroxyprogesterone (17OHP) in the blood of newborns, allowing rapid diagnostic confirmation and institution of therapy. The implementation of neonatal screening is an advance, but the control of pediatric patients with 21OH-D is complex and must always be individualized. Conclusion: The institution of newborn screening programs for CAH has benefits for the prognosis of children with 21OH-D. Its management is multi-professional, individualized and still a challenge even for the specialist. Wide dissemination of knowledge about the disease is desirable to allow better management of these children, especially girls with the disease who have atypical genitalia.

Actn3 gene polymorphism and factors associated with functional performance in elderly women assisted in primary health care / Polimorfismo do gene actn3 e os fatores associados ao desempenho funcional de idosas atendidas na atenção primária em saúde

ABSTRACT Objective: To analyze potential influences of the R/X genetic polymorphism of the ACTN3 gene, as well as of anthropometric and metabolic characteristics on the functional performance of elderly women assisted in primary health care. Method: One hundred and forty-one elderly women were assessed in terms of anthropometric, metabolic and functional aspects, in addition to clinical, cognitive and demographic characteristics. Allele and genotype frequencies of ACTN3 gene polymorphism were determined. Results: 141 elderly women (68.30 ± 6.18 years) were evaluated. No significant differences (p > 0.05) were observed between the RR and RX/XX genotypes in the elderly women's functional performance, anthropometric or metabolic characteristics. The TUG test completion time showed positive correlations with age, body mass index, waist circumference, and fat percentage (s = 0.315; p < 0.001; s = 0.238; p = 0.005; s = 0.174; p = 0.039; s = 0.207; p = 0.014), respectively. Negative correlations were found between the TUG test with absolute handgrip strength (s = - 0.314; p < 0.001) and relative handgrip strength (s = - 0.380; p < 0.001). Conclusion: In our study, there were no influences from ACTN3 gene polymorphisms on the functional performance of the elderly women, which is influenced by other factors.

RESUMO Objetivo: analisar as potenciais influências do polimorfismo genético R/X do gene ACTN3 e das características antropométricas e metabólicas no desempenho funcional de mulheres idosas atendidas na atenção primária em saúde. Método: Cento e quarenta e uma idosas foram avaliadas em relação as características antropométricas, metabólicas, funcionais, aspectos clínicos, cognitivos e demográficos. Foram determinadas as frequências de alelos e genótipos do polimorfismo do gene ACTN3. Resultados: 141 idosas (68,30 ± 6,18 anos) foram avaliadas. Não foram observadas diferenças significativas (p > 0,05) entre os genótipos RR e RX/XX no desempenho funcional, características antropométricas ou metabólicas das idosas. O tempo de realização do TUG apresentou correlações positivas com idade, índice de massa corporal, circunferência da cintura e percentual de gordura (s = 0,315; p < 0,001; s = 0,238; p = 0,005; s = 0,174; p = 0,039; s = 0,207; p = 0,014) respectivamente. Correlações negativas foram observadas entre o TUG com força de preensão manual absoluta (s = - 0,314; p < 0,001) e relativa (s = - 0,380; p < 0,001). Conclusão: Em nosso estudo, não foram observadas influências dos polimorfismos do gene ACTN3 no desempenho funcional das idosas, sendo este, influenciado por outros fatores.

sideRETRO: uma ferramenta de bioinformática dedicada à identificação deinserções polimórficas, germinativas ou somáticas, de pseudogenes processados / sideRETRO: a bioinformatics tool for identifying somatic and polymorphic insertions of processed pseudogenes

Os avanços metodológicos e instrumentais decorrentes do Projeto Genoma Humano formaram o arcabouço necessário para o surgimento das tecnologias de sequenciamento de DNA de Nova Geração, as quais se caracterizam por um custo reduzido, uma baixa demanda operacional e a produção de um grande volume de dados por experimento. Concomitantemente a isso, o aumento no poder de processamento computacional permitiu o desenvolvimento de análises genéticas em larga escala, de modo que, atualmente, é possível estudar características genômicas individualizadas e, até então, pouco ou nunca exploradas. Dentre essas características, aquelas relacionadas às variações estruturais em genomas têm recebido bastante atenção. Os pseudogenes processados, ou retrocópias, são variações estruturais causadas pela duplicação de genes codificadores mediante à transposição de seu RNA mensageiro maduro pela maquinaria enzimática de LINE- 1. As retrocópias podem estar fixadas, ou seja, presentes em todos os genomas de uma dada espécie, os quais são representados pela montagem modelo do genoma de referência, ou podem não estar fixadas, sendo polimórficas, germinativas ou somáticas. No entanto, o conhecimento acerca das retrocópias não fixadas ainda é limitado devido à falta de ferramentas de bioinformática dedicadas a sua identificação e anotação em dados de sequenciamento de DNA. Posto isso, este trabalho apresenta o sideRETRO um programa computacional especializado na detecção de pseudogenes processados ausentes do genoma de referência, mas presentes em dados de sequenciamento de genoma completo e exoma de outros indivíduos. Além de apontar para a presença de retrocópias não fixadas, o sideRETRO é capaz de anotar várias outras características relacionadas a esses evento, tais como: a coordenada genômica de inserção do pseudogene processado, a qual constitui o cromossomo, o ponto de inserção e a fita de DNA (líder or retardada); o contexto genômico do evento (exônico, intrônico ou intergênico); a genotipagem (presente ou ausente) e a haplotipagem (em homozigose ou heterozigose). Para atestar a eficiência da ferramenta, o sideRETRO foi executado para dados simulados e para dados reais validados experimentalmente por um grupo independente. Portanto, em resumo, nesta tese são descritos o desenvolvimento e o uso do sideRETRO uma ferramenta computacional robusta e eficiente, designada para identificar e anotar pseudogenes processados não fixados. Por fim, vale destacar que o sideRETRO preenche uma lacuna metodológica e possibilita novas hipóteses e investigações sistemáticas no campo de chamada de variantes estruturais

The methodological and instrumental advances resulting from the Human Genome Project have created the necessary framework to the emergence of Next Generation DNA sequencing technologies, which are characterized by a reduced cost, low operational demand and the generation of a large volume of data per experiment. Concomitantly with this, the increase in computational processing power has driven the development of large-scale genetic analyses, which allowed us to study individualized genomic traits little or never explored before. Among these characteristics, those related to structural variations in genomes have received much attention. Processed pseudogenes, or retrocopies, are structural variations caused by the duplication of coding genes through the transposition of their mature messenger RNA by the LINE-1 enzymatic machinery. Retrocopies can be fixed (i.e., present in all genomes of a given species and included into the assembly of the reference genome) or unfixed, being polymorphic, germinal or somatic. However, knowledge about unfixed retrocopies is still limited due to the lack of bioinformatics tools dedicated to their identification and annotation in DNA sequencing data. Therefore, this work presents sideRETRO a computer program specialized in the detection of processed pseudogenes absent from the reference genome, but present in whole genome and exome sequencing data from other individuals. In addition to pointing out the presence of unfixed retrocopies, sideRETRO is able to annotate several other characteristics related to these events, such as: the genomic coordinate of the processed pseudogene insetion, which constitutes the chromosome, the insertion point and the DNA strand (leader or retard); the genomic context of the event (exonic, intronic or intergenic); genotyping (present or absent) and haplotyping (homozygous or heterozygous). To certify the sideRETRO efficiency, it was run on simulated data and on real data experimentally validated by an independent group. Therefore, in summary, this thesis describes the development and use of sideRETRO a robust and efficient computational tool, designed to identify and annotate unfixed processed pseudogenes. Finally, it is worth noting that sideRETRO fills a methodological gap and allows new hypotheses and systematic investigations in the field of structural variant calling

Retrotransposon insertion polymorphism of the porcine esr gene and its association with production performances of Large White pigs / 生物工程学报

Estrogen receptor (esr) mediates the effects of estrogen on the expression of related genes, thereby regulating the growth and reproduction of mammals. To investigate the effect of retrotransposon insertion polymorphism (RIP) of the porcine esr gene on porcine growth performance, retrotransposon insertion polymorphism of the esr gene were predicted by comparative genomics and bioinformatics, and PCR was used to verify the insertion polymorphisms in different porcine breeds. Finally, the correlation analysis between the genotypes and performance of Large White pigs was conducted. The results showed that four retrotransposon polymorphic sites were identified in the esr1 and esr2 genes, which are esr1-SINE- RIP1 located in intron 2 of the esr1 gene, esr1-LINE-RIP2 and RIP3-esr1- SINE located in intron 5 of the gene, and esr2-LINE-RIP located in intron 1 of the esr2 gene, respectively. Among them, insertion of a 287 bp of SINE into intron 2 of the esr1 gene significantly affected (P<0.05) the live back fat thickness and 100 kg body weight back fat thickness of Large White pigs. Moreover, the live back fat thickness and back fat thickness at 100 kg body weight of homozygous with insertion (SINE+/+) was significantly greater than that of heterozygous with insertion (SINE+/-) and homozygous without insertion (SINE-/-). Therefore, esr1-SINE-RIP1 could be used as a molecular marker to assist the selection of deposition traits in Large White pigs.

Influencia del polimorfismo de CYP3A4 y CYP3A5 en la farmacocinética de tacrolimus en receptores de trasplante renal. Revisión narrativa / Influence of CYP3A4 and CYP3A5 polymorphism of the pharmacokinetics of tacrolimus in renal transplant recipients. Narrative review

El uso de inhibidores de calcineurina, en particular de tacrolimus como terapia inmunosupresora se ha generalizado a nivel mundial, permitiendo mejorar la tasa de sobrevida del injerto y la calidad de vida del paciente trasplantado. Con el acceso a los estudios de farmacogenética, los grupos de trasplante a nivel mundial se han visto motivados a realizar estudios genéticos que permitan interpretar la influencia de polimorfismos de genes como mTOR, PPP3CA, FK BP1A, FKBP2, y FOXP3, sin embargo, los más estudiados en la población trasplantada para optimizar la dosis de tacrolimus y ciclosporina son los polimorfismos del citocromo p450, CYP3A4 y CYP3A5.El objetivo de la presente revisión narrativa es examinar publicaciones recientes que estudien la relación entre el polimorfismo de CYP3A4/5 y el metabolismo de tacrolimus en pacientes trasplantados renales.Se revisó literatura reciente extraída de los sitios NCBI PubMed y PharmGKB.org en la que se hubiera investigado la influencia de los polimorfismos de CYP3A4/5 en el metabolismo de tacrolimus en trasplantados renales. Se identificó variaciones genéticas de CYP3A4/5 en pacientes trasplantados tratados con tacrolimus que permitirán a los médicos trasplantólogos dosificar de manera precisa el inmunosupresor. El uso de análisis farmacogenéticos permite determinar las variables genéticas del CYP3A4/5, y por lo tanto la toma de decisiones personalizadas en la dosis de inicio y de mantenimiento del inmunosupresor tacrolimus para alcanzar los niveles óptimos y con ello disminuir el riesgo de rechazo, de infecciones asociadas a inmunosupresión, y de toxicidad por el medicamento.

The use of the calcineurin inhibitor tacrolimus as immunosuppressive therapy, has become widespread world-wide, improving the graft's survival rate and the quality of life of the transplanted patient. With access to pharmacogenetic studies, transplant groups worldwide have been motivated to conduct genetic studies to inter-pret the influence of polymorphisms of genes such asmTOR, PPP3CA, FK BP1A, FKBP2, and FOXP3, however the most studied in the transplanted population to optimize the dose of tacrolimus and cyclosporine are those of cytochrome p450,CYP3A4 and CYP3A5. The objective of this narrative review is to examine recent publications studying the relationship betweenCYP3A4/5polymorphism, and tacrolimus metabolism in renal transplant patients. Literature extracted from the NCBI PubMed site and PharmGKB.org, from the past five years, which investigated the influence ofCYP3A4/5polymorphism on tacrolimus metabolism in renal transplants had been reviewed. Genetic variations ofCYP3A4/5 were identified in transplant patients treated with tacrolimus that will allow transplant physicians to dose the immunosuppressant accurately. The use of pharmacogenetic analyses makes it possible to determine the genetic polymorphisms ofCYP3A4/5, and therefore the decision-making cus-tomized at the starting and maintenance dose of the tacrolimus immunosuppressant to achieve optimal levels and thereby reduce the risk of rejection, immunosuppression-associated infections, and drug toxicity.

Influence of nutritional factors and the PON1 C(-107)T polymorphism on paraoxonase-1 activity in childhood / Influência de fatores nutricionais e do polimorfismo PON1 C(-107)T sobre a atividade da Paraoxonase 1 na infância

Abstract Objective: The cardioprotective enzyme paraoxonase-1 (PON1) suffers an important influence from genetic polymorphisms and nutritional factors. The aim of this study was to investigate the influence of diet, nutritional status, and the C(-107)T polymorphism on PON1 arylesterase activity in children. Methods: This was a cross-sectional study with 97 children, aged between 5 and 8 years, of both genders, from a pediatric outpatient clinic in southern Brazil. A sociodemographic, behavioral, and food consumption questionnaire was applied, and anthropometric measurements and laboratory blood samples were taken. PON1 arylesterase activity was measured by phenol extinction (U/mL), and DNA extraction and analysis of the PON1 C(-107)T polymorphism were performed. The Hardy-Weinberg equilibrium was tested with the chi-squared test and linear regression was used to estimate PON1 activity according to four adjustment models, with an acceptable error of 5%. Results: In the sample, the male gender accounted for 50.5%, 39.2% were 6 years of age, 54.5% had normal weight, and 51.5% had PON1 activity below the median (90.0, 15-30 U/mL). Genotype frequency was 54.6% (53/97), 31.0% (30/97), and 14.4% (14/97), respectively, for CT, CC, and TT, consistent with the Hardy-Weinberg equilibrium (p = 0.22). In the regression analysis, the model that included sociodemographic variables as well as frequency of consumption of fruits, vegetables, legumes, dairy products, and beans estimated a variability of 14.8% in PON1 activity combined with the PON1 C(-107)T polymorphism. Conclusions: During childhood, a good-quality diet with greater inclusion of healthy foods was important to predict the activity of the cardioprotective enzyme PON1 combined with the C(-107)T polymorphism of the PON1 gene.

Resumo Objetivo: A enzima cardioprotetora Paraoxonase 1 (PON1) sofre importante influência de polimorfismos genéticos e fatores nutricionais. O objetivo deste estudo foi investigar a influência da alimentação, do estado nutricional e do polimorfismo C(-107)T sobre a atividade arilesterase da PON1 em crianças. Métodos: Estudo transversal com 97 crianças entre 5 e 8 anos, de ambos os sexos, de um ambulatório de pediatria no sul do Brasil. Realizou-se questionário sociodemográfico, de comportamento e de consumo alimentar, medidas antropométricas e coleta de sangue em laboratório. A atividade arilesterase da PON1 foi mensurada pela extinção de fenol (U/mL), realizada extração do DNA e análise do polimorfismo PON1 C(-107)T. O equilíbrio de Hardy-Weinberg foi testado com qui-quadrado e usada regressão linear para estimar a atividade da PON1 segundo quatro modelos de ajuste, erro aceitável de 5%. Resultados: Na amostra o sexo masculino representou 50,5%, 39,2% tinham 6 anos, 54,5% eram eutróficos e 51,5% tinha atividade da PON1 inferior à mediana (90,0;15-30 U/ml). A frequência dos genótipos foi 54,6% (53/97), 31,0% (30/97) e 14,4% (14/97), respectivamente, para CT, CC e TT, estiveram em equilíbrio de Hardy-Weinberg (p = 0,22). Na análise de regressão o modelo que incluiu variáveis sociodemográficas, de frequência do consumo de frutas, verduras, legumes, laticínios e feijões estimou uma variabilidade de 14,8% na atividade da PON1 combinada ao polimorfismo PON1 C(-107)T. Conclusões: Na infância uma alimentação de boa qualidade, com maior participação de alimentos saudáveis foi importante para predizer a atividade da enzima cardioprotetora PON1 combinada ao polimorfismo C(-107)T do gene da PON1.

Analysis of filaggrin 2 gene polymorphisms in patients with atopic dermatitis

Abstract Background: Polymorphisms of the filaggrin 2 gene (rs 12568784 and rs 16899374) are associated with persistent atopic dermatitis in African American patients. Filaggrin 2 is a protein with a function similar to filaggrin and also encoded in the epidermal differentiation complex on chromosome 1q21. Objective: To evaluate the polymorphisms in the filaggrin 2 gene (rs 12568784 and rs 16899374) in children and adults with atopic dermatitis and to verify the association of these with the severity of the clinical picture, presence of other allergic diseases, and socio-demographic factors. Method: The study was carried out with patients and control group. Questionnaires were used to evaluate ethnicity, sex, age, family history, scoring, atopic dermatitis (SCORAD), among other parameters. Genotyping of the filaggrin 2 gene was performed by real-time polymerase chain reaction. Results: Forty-eight patients and 83 controls were evaluated. No correlation was found between the variables studied in patients with atopic dermatitis and polymorphisms, no significant difference between the prevalence of polymorphisms in the patients and in the control group p > 0.05. Study limits: The exclusive use of self-reported ethnicity information and the sample size. Results: The results of this work can be an incentive for the study of the polymorphisms in atopic dermaititis, considering the characteristic of the Brazilian multi ethnic population. Conclusion: This is an unpublished work in Brazil and the first study in the world to have a control group to evaluate alterations in the gene of filaggrin 2.

Polimorfismo +405G> C del gen del factor de crecimiento de endotelio vascular en población cubana / Vascular Endothelial Growth Factor gene +405G> C polymorphism in the Cuban population

Introducción: El factor de crecimiento endotelial vascular (VEGF) es una proteína involucrada en la proliferación y migración celular del endotelio vascular, en cuyo gen se ha reportado el polimorfismo +405G>C. Se reconoce que no existen reportes genéticos poblacionales de esta variante en Cuba, que permitan caracterizar los perfiles inmunogenéticos a nivel molecular, para su aplicación en estudios de asociación alélica. Objetivo: Describir las frecuencias génicas y genotípicas del polimorfismo VEGF (+405 G>C) en la población cubana. Material y Métodos: Se realizó un estudio observacional, descriptivo, transversal, entre octubre de 2017 y marzo de 2018 en 162 neonatos cubanos, de ambos sexos y sanos, para el pesquisaje neonatal de enfermedades metabólicas, cuyas muestras biológicas se conservaban en el banco de ADN del Centro Nacional de Genética Médica. La caracterización molecular de los genotipos fue realizada mediante un PCR-ARMS. Se utilizó el software GENEPOP 4.4 y el paquete estadístico STATISTICA 8.0 para los cálculos de las frecuencias génicas y genotípicas. Resultados: La población no se ajustó al modelo de equilibrio de Hardy Weinberg para el gen evaluado. Las frecuencias génicas estimadas para el polimorfismo VEGF (+405 G>C) fueron de 0,33 para el alelo G y de 0,67 para el alelo C. El cálculo de las frecuencias genotípicas resultó en 0,14, 0,37 y 0,49, para las variantes GG, GC y CC, respectivamente. Conclusiones: Las frecuencias alélicas VEGF.C fueron superiores a la del alelo VEGF.G, siendo el genotipo VEGF.GG el de menor representación en el conjunto estudiado(AU)

Introduction: The vascular endothelial growth factor (VEGF) is a protein involved in the proliferation and cell migration of the vascular endothelium. In its gene, +405G>C Polymorphism has been reported. There are no population genetic reports of this variant in Cuba that allow the characterization of immunogenetic profiles at a molecular level for its application to allelic association studies. Objectives: To describe the genic and genotypic frequencies of the VEGF (+405 G>C) polymorphism in the Cuban population. Material and Methods: A descriptive cross-sectional observational study was carried out from October 2017 to March 2018 in 162 Cuban healthy newborns of both sexes for the neonatal screening for metabolic diseases, whose biological samples were conserved in the DNA bank of the National Center for Medical Genetics. The molecular characterization of the genotypes was carried out using a PCR-ARMS. The GENEPOP 4.4 software and the statistical software package STATISTICA 8.0 were used for the analysis of genic and genotypic frequencies. Results: The population did not adjust to the Hardy-Weinberg equilibrium model for the gene evaluated. The estimated gene frequencies of VEGF +405 G> C polymorphism were 0.33 for the G allele and 0.67 for the C allele. The calculation of the genotypic frequencies resulted in 0.14, 0.37 and 0.49, for the variants GG, GC and CC, respectively. Conclusions: The allelic frequencies of VEGF.C were higher than the frequencies of the VEGF.G allele, being the VEGF GG the least represented genotype in the group studied(AU)

Influence of Angiotensin-converting Enzyme Insertion/Deletion Gene Polymorphism in Progression of Chagas Heart Disease

Abstract INTRODUCTION: Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi. One-third of infected patients will develop the cardiac form, which may progress to heart failure (HF). However, the factors that determine disease progression remain unclear. Increased angiotensin II activity is a key player in the pathophysiology of HF. A functional polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with plasma enzyme activity. In CD, ACE inhibitors have beneficial effects supporting the use of this treatment in chagasic cardiomyopathy. METHODS: We evaluated the association of ACE I/D polymorphism with HF, performing a case-control study encompassing 343 patients with positive serology for CD staged as non-cardiomyopathy (stage A; 100), mild (stage B1; 144), and severe (stage C; 99) forms of Chagas heart disease. For ACE I/D genotyping by PCR, groups were compared using unconditional logistic regression analysis and adjusted for nongenetic covariates: age, sex, and trypanocidal treatment. RESULTS: A marginal, but not significant (p=0.06) higher prevalence of ACE I/D polymorphism was observed in patients in stage C compared with patients in stage A. Patients in stage C (CD with HF), were compared with patients in stages A and B1 combined into one group (CD without HF); DD genotype/D carriers were prevalent in the HF patients (OR = 2; CI = 1.013.96; p = 0.04). CONCLUSIONS: Our results of this cohort study, comprising a population from the Northeast region of Brazil, suggest that ACE I/D polymorphism is more prevalent in the cardiac form of Chagas disease with HF.

Development of nuclear SSR and chloroplast genome markers in diverse Liriodendron chinense germplasm based on low-coverage whole genome sequencing

BACKGROUND: Liriodendron chinense ranges widely in subtropical China and northern Vietnam; however, it inhabits several small, isolated populations and is now an endangered species due to its limited seed production. The objective of this study was to develop a set of nuclear SSR (simple sequence repeats) and multiple chloroplast genome markers for genetic studies in L. chinense and their characterization in diverse germplasm. RESULTS: We performed low-coverage whole genome sequencing of the L. chinense from four genotypes, assembled the chloroplast genome and identified nuclear SSR loci by searching in contigs for SSR motifs. Comparative analysis of the four chloroplast genomes of L. chinense revealed 45 SNPs, 17 indels, 49 polymorphic SSR loci, and five small inversions. Most chloroplast intraspecific polymorphisms were located in the interspaces of single-copy regions. In total, 6147 SSR markers were isolated from low-coverage whole genome sequences. The most common SSR motifs were dinucleotide (70.09%), followed by trinucleotide motifs (23.10%). The motif AG/TC (33.51%) was the most abundant, followed by TC/AG (25.53%). A set of 13 SSR primer combinations were tested for amplification and their ability to detect polymorphisms in a set of 109 L. chinense individuals, representing distinct varieties or germplasm. The number of alleles per locus ranged from 8 to 28 with an average of 21 alleles. The expected heterozygosity (He) varied from 0.19 to 0.93 and the observed heterozygosity (Ho) ranged from 0.11 to 0.79. CONCLUSIONS: The genetic resources characterized and tested in this study provide a valuable tool to detect polymorphisms in L. chinense for future genetic studies and breeding programs.

Influence of Polymorphism of Vitamin D Receptor (Fok I) on Hypertension

Abstract Evidence suggests that polymorphisms in the gene encoding a vitamin D receptor might affect blood pressure. The objective of this systematic review was to investigate the association between hypertension and vitamin D receptor (Fok I) gene polymorphism. A literature search was performed according to the PRISMA guidelines using the MEDLINE®/PubMed, Scopus, Cochrane Library CENTRAL, SciELO, and LILACS databases. The quality of case-control or cohort studies and studies based on cross-sectional methodology was evaluated using the Newcastle-Ottawa Scale and the protocol of Loney and coauthors [25], respectively. In this systematic literature search, 215 publications were identified, of which 10 were analyzed, including seven case-control studies, two cross-sectional studies, and one cohort study. The association between Fok I polymorphism and hypertension was reported in 60% of the publications and the risk for hypertension was shown to be related to FF and ff genotypes. In addition, Fok I polymorphism was shown to increase plasma renin activity, which plays an important role in regulating blood pressure. However, no association was observed between Fok I polymorphism and serum vitamin D levels. In conclusion, Fok I polymorphism plays an important role in hypertension.

Human platelet antigen-3 polymorphism as a risk factor for rheumatological manifestations in hepatitis C

Abstract INTRODUCTION: Hepatitis C virus (HCV) infection is involved in the pathogenesis of autoimmune and rheumatic disorders. Although the human platelet antigens (HPA) polymorphism are associated with HCV persistence, they have not been investigated in rheumatological manifestations (RM). This study focused on verifying associations between allele and genotype HPA and RM in patients with chronic hepatitis C. METHODS: Patients (159) with chronic hepatitis C of both genders were analyzed. RESULTS: Women showed association between HPA-3 polymorphisms and RM. CONCLUSIONS: An unprecedented strong association between rheumatological manifestations and HPA-3 polymorphism, possibly predisposing women to complications during the disease course, was observed.

The APOB rs693 polymorphism impacts the lipid profile of Brazilian older adults

The apolipoprotein B (APOB) gene contains several polymorphic sites described as risk modifiers for cardiovascular events. The objective of this study was to verify the association of the classic APOB Xba I polymorphism (rs693) with atherosclerotic risk factors in a segment of the Brazilian elderly population considering their usual dietary intake. Clinical and biochemical characteristics as well as total caloric and fat intake data were determined from 644 elderly individuals. Polymorphism analysis was performed by conventional polymerase chain reaction followed by enzyme restriction. Statistical analyses compared measures and proportions according to different APOB genotypic combinations. Statistically significant association was found between Xba I polymorphism and serum LDL, total cholesterol, and total lipid levels, with important elevations among T homozygotes compared to the other genotypes. There was homogeneity in all other parameters analyzed (including intake pattern), with a tendency for reduced levels of circulating apolipoprotein B among TT individuals. Our results pointed out that genetic variation in APOB affected the lipemic profile of elderly individuals in a context not biased by diet, generating a pattern suggestive of secretory disorder of lipoprotein particles, with possible implication in atherosclerotic risk.

Polimorfismo de los antígenos leucocitarios humanos en receptores cubanos de trasplante relacionado de progenitores hematopoyéticas / Polymorphism of human leukocyte antigens in Cuban recipients of related hematopoietic stem cell transplants

Introducción: El trasplante relacionado de células progenitoras hematopoyéticas (TCPH) es una alternativa terapéutica curativa para los pacientes con ciertos tipos de hemopatías o de inmunodeficiencias, en la que se selecciona como donante a un familiar del receptor. Objetivo: Caracterizar el sistema de antígenos leucocitarios humanos (HLA) en receptores de TCPH relacionado. Métodos: Se realizó un estudio descriptivo y transversal en el departamento de Histocompatibilidad del Instituto de Hematología e Inmunología desde enero 2013 hasta diciembre de 2015. Se tipificaron 75 genes HLA mediante la técnica de reacción en cadena de la polimerasa con cebadores de secuencia específico, de baja resolución a 117 pacientes con criterio de TCPH. Para el análisis inmunogenético se empleó el programa Arlequín 3.5.2.2. Resultados: Fueron más frecuentes los genes HLA-A*02, HLA-B*35, HLA-DQB1*03, HLA-DRB1*03 y HLA-DRB1*04, los haplotipos de dos loci HLA-A*02 B*35, HLA-DQB1*03 DRB1*04 y el haplotipo extendido HLA-A*03 B*07 DQB1*06 DRB1*15. Conclusiones: Los genes del sistema HLA en pacientes cubanos candidatos a TCPH relacionado presentaron frecuencias similares a las descritas en poblaciones generales de Cuba y el mundo, aunque con características distintivas en algunos genes y haplotipos(AU)

Introduction: Related hematopoietic progenitor cell (TCPH) transplantation is a curative therapeutic alternative for patients with certain types of hemopathies or immunodeficiencies, in which a recipient family member is selected as a donor. Objective: To characterize the human leukocyte antigen (HLA) system in related TCPH receptors. Methods: A descriptive and cross-sectional study was conducted in the Histocompatibility department of the Institute of Hematology and Immunology from January 2013 to December 2015. 75 HLA genes were typed using the polymerase chain reaction technique with specific sequence primers, from Low resolution to 117 patients with TCPH criteria. For the immunogenetic analysis, the Harlequin 3.5.2.2 program was used. Results: The genes HLA-A * 02, HLA-B * 35, HLA-DQB1 * 03, HLA-DRB1 * 03 and HLA-DRB1 * 04, the haplotypes of two HLA-A * 02 B * 35 loci were more frequent , HLA-DQB1 * 03 DRB1 * 04 and the extended haplotype HLA-A * 03 B * 07 DQB1 * 06 DRB1 * 15. Conclusions: The genes of the HLA system in Cuban patients related to TCPH presented frequencies similar to those described in general populations of Cuba and the world, although with distinctive characteristics in some genes and haplotypes(AU)

Can the genetic polymorphisms of the folate metabolism have an influence in the polycystic ovary syndrome?

ABSTRACT Objective To investigate the association of the genetic variants of the folate metabolism genes (MTHFR C677T; MTHFR A1298C; MTR A2756G; MTRR A66G and RFC-1 A80G) with the development of polycystic ovary syndrome (PCOS). Subjects and methods This study included 203 women (99 women with PCOS and 104 controls). The genotyping was performed by PCR-RFLP. Chi-squared test and multiple logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the SNPstat program. The results were presented in odds ratio (OR) and confidence interval of 95% (CI-95%), with a significance level of 5% (p ≤ 0.05). Results The genotypic distribution of the RFC-1 A80G polymorphism showed significant difference between the two groups, showing that the heterozygous genotype (AG genotype) was most frequent in controls. The polymorphic homozygous (GG genotype) of MTRR A66G polymorphism were most frequent in controls. The T-C haplotype MTHFR C677T and A1298C polymorphisms were more frequent in the control group (OR = 0.19; CI 95% — 0.04 to 0.93 e p = 0.042). The multivariate analysis evidenced that family history of PCOS was more frequent in the PCOS group (OR = 3.29; CI 95% — 1.48 to 7.31; p = 0.003). Conclusion In our casuistry, the polymorphic homozygous of MTRR A66G polymorphism gene and heterozygous of RFC-1 A80G polymorphism gene, the haplotype T-C C677T and A1298C polymorphisms of MTHFR gene, can be associated with protective factors for the disease.

Polymorphisms of the renin-angiotensin system are not associated with overweight and obesity in a general adult population

ABSTRACT Objective The increased prevalence of obesity and associated comorbidities, such as cardiovascular and metabolic diseases, has gained attention worldwide, and the renin-angiotensin system (RAS) has been pointed out as a possible link. Thus, the present study aimed to verify the possible association between angiotensinogen (AGT) or angiotensin-converting enzyme (ACE) polymorphisms with overweight and obesity in adults. Subjects and methods The present investigation was a population-based cross-sectional study including 1,567 individuals from an urban area in Brazil. Anthropometric, clinical and biochemical parameters were evaluated, and all individuals were genotyped for the ACE I/D and AGT M/T polymorphisms. Results The prevalence of overweight was higher among men, whereas obesity was more prevalent among women. However, the frequency of ACE or AGT polymorphisms was similar among body mass index (BMI) categories. In addition, the mean age-adjusted BMI averages did not change significantly for ACE or AGT polymorphisms, regardless of sex or BMI category. The age-adjusted BMI average for the combination of ACE and AGT genotypes evidenced no significant differences regardless of sex or BMI categories. Results were similar when BMI was replaced by waist circumference (WC). Conclusions We were not able to find any associations between BMI and WC (overweight/obesity) and ACE and AGT polymorphisms, indicating that the RAS system might not be involved in overweight and obesity, at least based on genetic backgrounds. However, further studies must measure RAS components to elucidate this question.

Searching for mutations in the HNF1B gene in a Brazilian cohort with renal cysts and hyperglycemia

ABSTRACT Objective To verify the presence of variants in HNF1B in a sample of the Brazilian population selected according to the presence of renal cysts associated with hyperglycemia. Subjects and methods We evaluated 28 unrelated patients with clinical suspicion of HNF1B mutation because of the concomitant presence of diabetes mellitus (DM) or prediabetes and renal cysts. Genotyping was accomplished using Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). In positive cases, available relatives were recruited. Results We found two patients with HNF1B mutations. The first presented the variant p.Pro328Leufs*48(c.983delC) and had DM, renal cysts, and hypomagnesemia. The second presented a heterozygous whole gene deletion in HNF1B, DM, renal cysts, body and tail pancreatic agenesis, and hypomagnesemia; this alteration was also found in his two siblings and his father. Conclusion The recruitment of suspected cases of HNF1B gene mutations in Brazilians due to hyperglycemia and renal cysts presents two positive cases. Our cases contribute to the annotation of clinical and biochemical phenotypes of this rare form of maturity-onset diabetes of the young (MODY).

Paraoxonase 1 serum activity in women: the effects of menopause, the C(-107)T polymorphism and food intake

ABSTRACT Objective The aims of this study were to investigate changes in serum paraoxonase 1 (PON1) activity in women at the pre and postmenopausal stages and its association with the PON1 C(-107)T polymorphism and food intake profile. Subjects and methods A cross-sectional study with female patients aged between 35 and 59 years old was conducted. Women were divided into two groups: premenopausal (n = 40) and postmenopausal (n = 36). Women enrolled in the study had serum PON1, total cholesterol, HDL, LDL, glucose and HbA1c, as well as the BMI measured. Additionally, women were genotyped for the PON1 T(-107)C polymorphism and the food intake profile was obtained through interview. Results Glucose (p = 0.03), HbA1c (p = 0.002) and total cholesterol (p = 0.002)concentrations were higher in post than premenopausal women, however PON1 activity was not different (p > 0.05). Carriers of the C allele had higher PON1 activity (CC: 88.9 ± 6.5 U/mL and CT: 79.9 ± 4.7 U/mL) than women of the TT genotype (66.6 ± 5.9 U/mL) (p < 0.05). However, the model predicting PON1 activity was slightly better when genotype, total fat and cholesterol content in the diet were all included. Conclusion In sum, we observed that the PON1 C(-107)T genotype was the major regulator of PON1 activity, and menopause had no effect on PON1 activity. The lipid and glycemic profile were altered in postmenopausal women.