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1.
Braz. j. biol ; 80(1): 39-46, Feb. 2020. graf
Artigo em Inglês | LILACS (Américas) | ID: biblio-1089293

RESUMO

Abstract The current study aimed to assess whether the A122V causal polymorphism promotes alterations in the functional and structural proprieties of the CXC chemokine receptor type 1 protein (CXCR1) of cattle Bos taurus by in silico analyses. Two amino acid sequences of bovine CXCR1 was selected from database UniProtKB/Swiss-Prot: a) non-polymorphic sequence (A7KWG0) with alanine (A) at position 122, and b) polymorphic sequence harboring the A122V polymorphism, substituting alanine by valine (V) at same position. CXCR1 sequences were submitted as input to different Bioinformatics' tools to examine the effects of this polymorphism on functional and structural stabilities, to predict eventual alterations in the 3-D structural modeling, and to estimate the quality and accuracy of the predictive models. The A122V polymorphism exerted tolerable and non-deleterious effects on the polymorphic CXCR1, and the predictive structural model for polymorphic CXCR1 revealed an alpha helix spatial structure typical of a receptor transmembrane polypeptide. Although higher variations in the distances between pairs of amino acid residues at target-positions are detected in the polymorphic CXCR1 protein, more than 97% of the amino acid residues in both models were located in favored and allowed conformational regions in Ramachandran plots. Evidences has supported that the A122V polymorphism in the CXCR1 protein is associated with increased clinical mastitis incidence in dairy cows. Thus, the findings described herein prove that the replacement of the alanine by valine amino acids provokes local conformational changes in the A122V-harboring CXCR1 protein, which could directly affect its post-translational folding mechanisms and biological functionality.


Resumo O presente estudo objetivou avaliar se o polimorfismo causal A122V promove alterações nas propriedades funcionais e estruturais da proteína receptora de quimiocina CXC do tipo 1 (CXCR1) de bovino Bos taurus por análises in silico. Duas sequências de aminoácidos da CXCR1 bovina foram selecionadas a partir do banco de dados UniProtKB/Swiss-Prot: a) sequência não-polimórfica (A7KWG0) contendo alanina (A) na posição 122, e b) sequência polimórfica carreando o polimorfismo A122V, causando a substituição de alanina por valina (V) na mesma posição. As sequências CXCR1 foram analisadas por diferentes ferramentas de Bioinformática para examinar o efeito desse polimorfismo sobre sua estabilidade, função e estrutura, predizer eventuais alterações na sua modelagem estrutural 3-D, bem como estimar a qualidade dos modelos preditos. O polimorfismo A122V exerceu efeitos toleráveis e não-deletérios sobre a CXCR1 polimórfica, apresentando um modelo estrutural de alfa-hélice típico de uma proteína receptora transmembranar para ambas as proteínas. Embora maiores variações nas distâncias entre os pares de aminoácidos nas posições-alvo tenham sido detectadas na proteína polimórfica, mais do que 97% dos aminoácidos em ambos os modelos foram situados em regiões ditas favoráveis e permitidas nos diagramas de Ramachandran. Evidências sustentam que o polimorfismo de nucleotídeo único A122V na proteína receptora CXCR1 está associado à aumentada incidência de mastite clínica em vacas leiteiras. Assim, as descobertas descritas aqui comprovam que a substituição do aminoácido alanina por valina provoca mudanças conformacionais locais na proteína CXCR1 polimórfica, que podem estar diretamente afetando seus mecanismos de enovelamento pós-traducionais e sua função biológica.


Assuntos
Animais , Feminino , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-8A , Bovinos , Sequência de Aminoácidos
2.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-782242

RESUMO

Donor cell leukemia (DCL), a rare but fatal complication arising from allogenic stem cell transplantation, is a complex disease associated with multiple pathophysiological processes. Specific diagnosis of DCL distinct from relapsed leukemia is important owing to its implications in setting up therapeutic approaches. Fluorescence in situ hybridization (FISH), short tandem repeat (STR), variable number tandem repeat (VNTR) tests, or informative single nucleotide polymorphism (SNP) analysis can be used to confirm the origin of leukemic cells from donor cells. Here, we report a case of DCL in a female patient after allogeneic peripheral stem cell transplantation from a male donor for the treatment of acute promyelocytic leukemia (APL) with PML-RARA. DCL developed 6 years after stem cell transplantation and leukemic cells of donor origin were confirmed by the presence of Y chromosome on the X/Y FISH analysis of bone marrow aspirate specimen. This is the first case of DCL reported in an APL patient in Korea.


Assuntos
Medula Óssea , Diagnóstico , Feminino , Fluorescência , Humanos , Hibridização In Situ , Coreia (Geográfico) , Leucemia , Leucemia Promielocítica Aguda , Masculino , Repetições de Microssatélites , Transplante de Células-Tronco de Sangue Periférico , Polimorfismo de Nucleotídeo Único , Transplante de Células-Tronco , Sequências de Repetição em Tandem , Doadores de Tecidos , Cromossomo Y
3.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-782227

RESUMO

For the past three decades, more than a thousand of genetic studies have been performed to find out the genetic variants responsible for the risk of asthma. Until now, all of the discovered single nucleotide polymorphisms have explained genetic effects less than initially expected. Thus, clarification of environmental factors has been brought up to overcome the ‘missing’ heritability. The most exciting solution is epigenesis because it intervenes at the junction between the genome and the environment. Epigenesis is an alteration of genetic expression without changes of DNA sequence caused by environmental factors such as nutrients, allergens, cigarette smoke, air pollutants, use of drugs and infectious agents during pre- and post-natal periods and even in adulthood. Three major forms of epigenesis are composed of DNA methylation, histone modifications, and specific microRNA. Recently, several studies have been published on epigenesis in asthma and allergy as a powerful tool for research of genetic heritability in asthma albeit epigenetic changes are at the starting point to obtain the data on specific phenotypes of asthma. In this presentation, we mainly review the potential role of DNA CpG methylation in the risk of asthma and its sub-phenotypes including nonsteroidal anti-inflammatory exacerbated respiratory diseases.


Assuntos
Poluentes Atmosféricos , Alérgenos , Aspirina , Asma , Sequência de Bases , Metilação de DNA , DNA , Epigenômica , Genoma , Código das Histonas , Hipersensibilidade , Metilação , MicroRNAs , Fenótipo , Polimorfismo de Nucleotídeo Único , Fumaça , Produtos do Tabaco
4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781289

RESUMO

OBJECTIVE@#To assess the association of JAG2 gene single nucleotide polymorphisms with the occurrence of nonsyndromic cleft lip with or without cleft palate (NSCLP) among northwest Chinese population.@*METHODS@#A case-control study was carried out on 301 NSCLP patients and 304 healthy controls. An iMLDR(TM) genotyping technique was used to detect three single nucleotide polymorphisms (SNPs) [rs741859 (T/C), rs11621316 (A/G) and rs1057744(C/T)] of the JAG2 gene. Allelic and genotypic frequencies and haplotypic distribution among the two groups were compared.@*RESULTS@#A significant difference was found in the frequency of C and T alleles for rs741859 between the two groups. The CT genotype of rs741859 could significantly reduce the risk for NSCLP to 65% (P 0.8), whose distribution difference between the two groups was not statistically significant (P> 0.05).@*CONCLUSION@#The CT genotype of the JAG2 gene rs741859 may confer a protective effect for NSCLP among northwest Chinese population.


Assuntos
Estudos de Casos e Controles , China , Fenda Labial , Genética , Fissura Palatina , Genética , Frequência do Gene , Genótipo , Humanos , Proteína Jagged-2 , Genética , Polimorfismo de Nucleotídeo Único
5.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-786073

RESUMO

OBJECTIVE: Total ceramide concentrations are linked with increased insulin resistance and cardiac dysfunction. However, recent studies have demonstrated that plasma concentrations of specific very-long-chain fatty ceramides (C24:0 and C22:0) are associated with a reduced incidence of coronary heart disease and all-cause mortality. We hypothesized that specific genetic loci are associated with plasma C22:0 and C24:0 concentrations.METHODS: Heritability and genome-wide association studies of plasma C24:0 and C22:0 ceramide concentrations were performed among 2,217 participants in the Framingham Heart Study Offspring Cohort, adjusting for cardiovascular risk factor covariates and cardiovascular drug treatment.RESULTS: The multivariable-adjusted heritability for C22:0 and C24:0 ceramides was 0.42 (standard error [SE], 0.07; p=1.8E-9) and 0.25 (SE, 0.08; p=0.00025), respectively. Nineteen single nucleotide polymorphisms (SNPs), all on chromosome 20, significantly associated with C22:0 concentrations; the closest gene to these variants was SPTLC3. The lead SNP (rs4814175) significantly associated with 3% lower plasma C22:0 concentrations (p=2.83E-11). Nine SNPs, all on chromosome 20 and close to SPTLC3, were significantly associated with C24:0 ceramide concentrations. All 9 were also significantly related to plasma C22:0 levels. The lead SNP (rs168622) was significantly associated with 10% lower plasma C24:0 ceramide concentrations (p=9.94E-09).CONCLUSION: SNPs near the SPTLC3 gene, which encodes serine palmitoyltransferase long chain base subunit 3 (SPTLC3; part of the enzyme that catalyzes the rate-limiting step of de novo sphingolipid synthesis) were associated with plasma C22:0 and C24:0 ceramide concentrations. These results are biologically plausible and suggest that SPTLC3 may be a potential therapeutic target for C24:0 and C22:0 ceramide modulation.


Assuntos
Doenças Cardiovasculares , Ceramidas , Cromossomos Humanos Par 20 , Estudos de Coortes , Doença das Coronárias , Loci Gênicos , Estudo de Associação Genômica Ampla , Genômica , Coração , Incidência , Resistência à Insulina , Mortalidade , Plasma , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Serina C-Palmitoiltransferase
6.
Horiz. méd. (Impresa) ; 19(4): 14-19, Dic. 2019. tab
Artigo em Espanhol | LILACS (Américas), LIPECS | ID: biblio-1048783

RESUMO

Objetivo: Analizar la asociación de los polimorfismos de un solo nucleótido (SNP) rs941798 y rs914458 del gen PTPN1 con la diabetes tipo 2 en familias peruanas de Lima. Materiales y métodos: Veintitrés tríos familiares fueron captados en el Hospital Nacional Arzobispo Loayza. Se extrajeron muestras de sangre periférica para obtener el ADN y luego las frecuencias alélicas y genotípicas de los SNP. La genotipificación de los SNP se realizó mediante secuenciación. El análisis de asociación basado en familias entre los SNP y la diabetes tipo 2 se realizó con el programa FBAT. Resultados: Se observaron los 3 genotipos posibles para cada SNP, rs941798 (A>G) y rs914458 (G>C). Las pruebas de asociación basada en familias a nivel alélico mostraron al alelo A del SNP rs941798 asociado a la diabetes tipo 2 (p = 0.023) bajo uno de los modelos evaluados; no obstante, tras la corrección de Bonferroni para comparaciones múltiples, esta asociación se perdió. No se evidenció asociación entre los SNP y la enfermedad en ningún nivel (alélico, genotípico o haplotípico). Conclusiones: No se encontraron evidencias de asociación significativa entre los SNP rs941798 y rs914458 del gen PTPN1 con la DT2 en familias peruanas de Lima, en ninguno de los niveles estudiados (alélico, genotípico y haplotípico).


Objective: To analyze the association that PTPN1 gene single nucleotide polymorphisms (SNPs) rs941798 and rs914458 have with type 2 diabetes in Peruvian families from Lima. Materials and methods: Twenty-three (23) families consisting of three members each were recruited at the Hospital Nacional Arzobispo Loayza. Peripheral blood samples were collected to obtain the DNA, and then the allele and genotype frequencies of the SNPs. SNP genotyping was performed using the sequencing method. The family-based analysis of the association between SNPs and type 2 diabetes was conducted using the family-based association test (FBAT) program. Results: Three (3) possible genotypes were observed for each SNP, i.e. rs941798 (A>G) and rs914458 (G>C). In one of the assessed models, the family-based association tests showed at the allele level that allele A of SNP rs941798 is associated with type 2 diabetes (p = 0.023). However, after using the Bonferroni correction for multiple comparisons, this association was lost. No association was demonstrated between the SNPs and the disease at any level (allele, genotype or haplotype). Conclusions: No evidence of significant association was found between PTPN1 gene SNPs rs941798 and rs914458 and type 2 diabetes at the studied levels (allele, genotype or haplotype) in Peruvian families from Lima.


Assuntos
Humanos , Diabetes Mellitus Tipo 2 , Marcadores Genéticos , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 1
7.
An. bras. dermatol ; 94(4): 429-433, July-Aug. 2019. tab
Artigo em Inglês | LILACS (Américas) | ID: biblio-1038308

RESUMO

Abstract: Background: Behçet disease is a prototypical systemic autoimmune disease, caused by a complex interplay between environmental and genetic factors. The transmembrane immunoglobulin and mucin domain-3 (TIM-3) is a distinct member of the TIM family that is preferentially expressed on Th1 cells and plays a role in Th1-mediated autoimmune or inflammatory diseases, such as Behçet disease. Objective: The aim of this study was to test the potential association between TIM-3 gene polymorphisms and Behçet disease. Methods: Two single-nucleotide polymorphisms of TIM-3 (rs9313439 and rs10515746) were genotyped in 212 patients with Behçet disease and 200 healthy controls. Typing of the polymorphisms was performed using multiplex PCR amplification. Results: There were no significant differences in allele and genotype frequencies between the Behçet disease patients and controls who were successfully genotyped. Similar results were also found after stratification by gender, age, or clinical features. Study limitations: Lack of studies on various racial or ethnic groups and small sample size. Conclusion: This study failed to demonstrate any association between the tested TIM-3 polymorphisms and Behçet disease.


Assuntos
Humanos , Masculino , Feminino , Adulto , Síndrome de Behçet/genética , Polimorfismo de Nucleotídeo Único , Receptor Celular 2 do Vírus da Hepatite A/genética , Estudos de Casos e Controles , Modelos Logísticos , Fatores de Risco , Medição de Risco , Alelos , Estudos de Associação Genética , Reação em Cadeia da Polimerase Multiplex , Frequência do Gene , Irã (Geográfico)
8.
Electron. j. biotechnol ; 40: 17-21, July. 2019. tab, ilus
Artigo em Inglês | LILACS (Américas) | ID: biblio-1053211

RESUMO

Background: Mastitis is one of the most serious diseases of dairy cattle, causing substantial financial losses. While predisposition to reduced somatic cell count in milk has been considered for in cattle breeding programs as the key indicator of udder health status, scientists are seeking genetic markers of innate immune response, which could be helpful in selecting cows with improved immunity to mastitis. Lipocalin-2 (LCN2) is a protein involved in the response of the immune system by eliminating iron ions which are necessary for the growth of pathogenic bacteria, so LCN2 may be considered as a natural bacteriostatic agent and could become a marker of infection. Results: A total of five SNPs were identified in LCN2 gene (one in the promoter, three in exon 1, and one in intron 1). A single haplotype block was identified. The locus g.98793763GNC was found to have a significant impact on protein levels in milk, and alleles of this locus were identified to have a significant positive dominance effect on this trait. None of the four analysed loci had a statistically significant impact on the milk yield, fat levels in milk or the somatic cell score. LCN-2 gene had no significant impact on the incidence of mastitis in the cows. Conclusions: Although the identified SNPs were not found to have any impact on the somatic cell count or the incidence of mastitis in cows, it seems that further research is necessary, covering a larger population of cattle, to confirm the association between lipocalin-2 and milk production traits and mastitis.


Assuntos
Animais , Bovinos , Polimorfismo Genético , Leite/imunologia , Lipocalina-2/genética , Mastite Bovina/genética , Haplótipos , Cruzamento , Polimorfismo de Nucleotídeo Único , Alelos , Lipocalina-2/química , Glândulas Mamárias Animais , Mastite Bovina/imunologia
9.
Autops. Case Rep ; 9(2): e2018084, Abr.-Jun. 2019. ilus, tab
Artigo em Inglês | LILACS (Américas) | ID: biblio-994660

RESUMO

JAK2 mutations are rare in de novo acute myeloid leukemia (AML), and JAK2-mutated acute myeloid leukemia (AML) patients usually have a previous history of myeloproliferative neoplasms (MPNs). Current advances in laboratory techniques, such as single nucleotide polymorphism array (SNPa) and next-generation sequencing (NGS), have facilitated new insight into the molecular basis of hematologic diseases. Herein, we present two cases of JAK2-mutated AML in which both SNPa and NGS methods added valuable information. Both cases had leukemogenic collaboration, namely, copy-neutral loss of heterozygosity (CN-LOH), detected on chromosome 9. One of the cases exhibited both JAK2 and IDH2 mutations, most likely having originated as an MPN with leukemic transformation, while the other case was classified as a de novo AML with JAK2, CEBPA, and FLT3 mutations.


Assuntos
Humanos , Feminino , Idoso , Leucemia Mieloide Aguda/diagnóstico , Análise de Sequência de DNA/instrumentação , Polimorfismo de Nucleotídeo Único , Citogenética/instrumentação
10.
Asia Pacific Allergy ; (4): e22-2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-750189

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common and complex chronic inflammatory disease of sinonasal mucosa. Even though the pathogenesis of CRS is multifactorial and still unclear, the role of cytokines especially interleukin-1 (IL-1) is being investigated worldwide in different population because of varying results obtained. OBJECTIVE: To study the association of IL-1 (A and B) gene polymorphisms with chronic rhinosinusitis with nasal polyp (CRSwNP) and without nasal polyp (CRSsNP), and other factors related. METHODS: This is a case-controlled study which include a total of 138 subjects recruited from Otorhinolaryngology-Head and Neck Surgery clinic in Hospital Universiti Sains Malaysia. Genotyping of the IL-1A (+4845G, +4845T) and IL-1B (−511C, −511T) were performed with restriction fragment length polymorphism analysis. RESULTS: There was a statistical significant association between IL-1B (−511C, −511T) polymorphism with CRSwNP and CRSsNP (p 0.95, and 0.254, respectively). CONCLUSION: This study indicates an association of IL-1B (−511C, −511T) polymorphism with CRSwNP and CRSsNP in our population, hence there is a possibility of IL-1B involvement in modulating pathogenesis of CRS. There was no significant association of IL-1A (+4845G, +4845T) polymorphism with CRSwNP and CRSsNP, and other factors related.


Assuntos
Aspirina , Asma , Estudos de Casos e Controles , Citocinas , Genótipo , Humanos , Hipersensibilidade , Interleucina-1 , Malásia , Membrana Mucosa , Pólipos Nasais , Pescoço , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-819035

RESUMO

OBJECTIVE@#To conduct genetic analysis in a fetus with complex translocation of four chromosomes.@*METHODS@#G-banded chromosome karyotype analysis, single nucleotide polymorphism array (SNP array) and fluorescence hybridization (FISH) were performed in a fetus with multiple malformations. Peripheral blood chromosome karyotype and FISH were also carried out for the parents.@*RESULTS@#The fetal amniotic fluid karyotype was 46, XY, t(12; 13)(q22; q32). SNP array analysis showed that there were 20 192 kb duplication at 1q42.13q44 and 13 293 kb deletion at 15q26.1q26.3 in the fetus. The results of karyotype and SNP array were inconsistent. FISH analyses on the parental peripheral blood samples demonstrated that the mother was a cryptic 46, XX, t(1; 15)(q42.1; q26.1) translocation. The fetus had inherited 46, XY, t(12; 13)(q22; q32) from his father and der(15)t(1; 15)(q42.1; q26.1) from his mother.@*CONCLUSIONS@#The 1q42.13q44 duplication and 15q26.1q26.3 deletion may have contributed to the abnormal sonographic features of the fetus. The combination of cytogenetic, SNP array and FISH techniques was beneficial for providing an accurate genetic counseling.


Assuntos
Aberrações Cromossômicas , Feminino , Feto , Anormalidades Congênitas , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Polimorfismo de Nucleotídeo Único , Translocação Genética
12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-819032

RESUMO

OBJECTIVE@#To assess the clinical application of single nucleotide polymorphism microarray (SNP array) in prenatal genetic diagnosis for fetuses with absent nasal bone.@*METHODS@#Seventy four fetuses with absent nasal bone detected by prenatal ultrasound scanning were recruited from Women's Hospital, Zhejiang University School of Medicine during June 2015 and October 2018. The chromosome karyotypes analysis and SNP array were performed. The correlation between absent fetal nasal bone and chromosome copy number variants was analyzed.@*RESULTS@#Among 74 fetuses, 19 were detected to have chromosomal abnormalities, including 16 cases of trisomy-21, 1 case of trisomy-18 and two cases of micro-deletion/duplication. Among 46 cases with isolated absence of nasal bone, 3 had trisomy-21, and 1 had a micro-duplication. Absence of nasal bone in association with nuchal translucency thickening had a higher rate of abnormal karyotypes compared with isolated absence of nasal bone (=32.27,<0.01).@*CONCLUSIONS@#Fetuses with absent nasal bone and nuchal translucency thickening are likely to have chromosome abnormalities, and SNP array testing is recommended to exclude the chromosome abnormalities.


Assuntos
Aberrações Cromossômicas , Feminino , Feto , Humanos , Osso Nasal , Anormalidades Congênitas , Análise de Sequência com Séries de Oligonucleotídeos , Padrões de Referência , Polimorfismo de Nucleotídeo Único , Genética , Gravidez , Primeiro Trimestre da Gravidez , Diagnóstico Pré-Natal , Métodos
13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-819031

RESUMO

OBJECTIVE@#To assess the clinical application of single nucleotide polymorphism microarray (SNP array) in patients with intellectual disability/developmental delay(ID/DD).@*METHODS@#SNP array was performed to detect genome-wide DNA copy number variants (CNVs) for 145 patients with ID/DD in Women's Hospital, Zhejiang University School of Medicine from January 2013 to June 2018. The CNVs were analyzed by CHAS software and related databases.@*RESULTS@#Among 145 patients, pathogenic chromosomal abnormalities were detected in 32 cases, including 26 cases of pathogenic CNVs and 6 cases of likely pathogenic CNVs. Meanwhile, 18 cases of uncertain clinical significance and 14 cases of likely benign were identified, no significant abnormalities were found in 81 cases (including benign).@*CONCLUSIONS@#SNP array is effective for detecting chromosomal abnormalities in patients with ID/DD with high efficiency and resolution.


Assuntos
Aberrações Cromossômicas , Variações do Número de Cópias de DNA , Estudo de Associação Genômica Ampla , Humanos , Deficiência Intelectual , Diagnóstico , Genética , Análise de Sequência com Séries de Oligonucleotídeos , Padrões de Referência , Polimorfismo de Nucleotídeo Único
14.
Chinese Medical Journal ; (24): 446-453, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-774833

RESUMO

BACKGROUND@#Adhesion, biofilm formation, yeast-hyphal transition, secretion of enzymes, and hemolytic activity are all considered important factors in Candida tropicalis infection. However, DNA sequence data for this pathogen are limited. In this study, the polymorphism and heterogeneity of genes agglutinin-like sequences (ALS)2, Lipase (LIP)1, LIP4, and secretory aspartyl proteinase tropicalis (SAPT)1-4 as well as the relationship between phenotype and genotype were analyzed.@*METHODS@#This study started in August 2013, and ended in July 2017. The complete length of ALS2, LIP1, LIP4, and SAPT1-4 of 68 clinical C. tropicalis isolates was sequenced. Single nucleotide polymorphisms (SNPs) as well as insertions and deletions (indels) were identified within these genes. In addition, phenotypic characteristics of the virulent factors, including adhesion and the secretion of aspartyl proteinases and phospholipases, were determined.@*RESULTS@#There were 73, 24, 17, 16, 13, and 180 SNPs in the genes LIP1, LIP4, SAPT1, SAPT2, SAPT3, and SAPT4, respectively. Furthermore, 209 SNPs were identified in total for the gene ALS2. Interestingly, large fragment deletions and insertions were also found in ALS2. Isolate FXCT 01 obtained from blood had deletions on all 4 sites and showed the lowest adhesion ability on the polymethylpentene surface. In addition, isolates with deletions in the regions 1697 to 1925 and 2073 to 2272 bp displayed relatively low abilities for adhesion and biofilm formation, and this phenotype correlated with the deletions found in ALS2. LIP1, SAPT4, and ALS2 displayed great heterogeneity among the isolates. Large deletions found in gene ALS2 appeared to be associated with the low ability of adhesion and biofilm formation of C. tropicalis.@*CONCLUSION@#This study might be useful for deeper explorations of gene function and studying the virulent mechanisms of C. tropicalis.


Assuntos
Aderência Bacteriana , Biofilmes , Candida tropicalis , Genética , Virulência , Lipase , Genética , Polimorfismo de Nucleotídeo Único , Virulência , Genética
15.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762171

RESUMO

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) has attracted a great deal of attention because of its association with severe asthma. However, it remains widely underdiagnosed in asthmatics as well as the general population. Upon pharmacological inhibition of cyclooxygenase 1 by NSAIDs, production of anti-inflammatory prostaglandin E2 and lipoxins ceases, while release of proinflammatory cysteinyl leukotrienes increases. To determine the underlying mechanisms, many studies have attempted to elucidate the genetic variants, such as single nucleotide polymorphisms, responsible for alterations of prostaglandins and leukotrienes, but the results of these genetic studies could not explain the whole genetic pathogenesis of NERD. Accordingly, the field of epigenetics has been introduced as an additional contributor to genomic alteration underlying the development of NERD. Recently, changes in CpG methylation, as one of the epigenetic components, have been identified in target tissues of NERD. This review discusses in silico analyses of both genetic and epigenetic components to gain a better understanding of their complementary roles in the development of NERD. Although the molecular mechanisms underlying NERD pathogenesis remain poorly understood, genetic and epigenetic variations play significant roles. Our results enhance the understanding of the genetic and epigenetic mechanisms involved in the development of NERD and suggest new approaches toward better diagnosis and management.


Assuntos
Anti-Inflamatórios não Esteroides , Asma , Simulação por Computador , Ciclo-Oxigenase 1 , Diagnóstico , Dinoprostona , Epigenômica , Genética , Leucotrienos , Lipoxinas , Metilação , Polimorfismo de Nucleotídeo Único , Prostaglandinas
16.
Yonsei Medical Journal ; : 651-658, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762095

RESUMO

PURPOSE: Genome-wide association studies (GWAS) have revealed that common variants on or near EDNRA, HDAC9, SOX17, RP1, CDKN2B-AS1, and RBBP8 genes are associated with intracranial aneurysm (IA) in European or Japanese populations. However, due to population heterogeneity, whether these loci are associated with IA pathogenesis in Chinese individuals is still unknown. The purpose of this study was to investigate associations among GWAS-identified loci and risk of IA in a Chinese population. MATERIALS AND METHODS: A total of 765 individuals (including 230 IA patients and 535 controls) were involved in this study. Twelve single nucleotide polymorphisms (SNPs) of candidate loci were genotyped using the Sequenom MassARRAY platform. Associations were analyzed using univariate or multivariate logistic regression analysis. RESULTS: SNPs in CDKN2B-AS1 (especially rs10757272) showed significant associations with IA in dominant and additive models [odds ratio (OR), 2.99 and 1.43; 95% confidence interval (CI), 1.44–6.24 and 1.10–1.86, respectively]. A SNP near HDAC9 (rs10230207) was associated with IA in the dominant model (OR, 1.42; 95% CI, 1.01–1.99). One SNP near RP1 (rs1072737) showed a protective effect on IA in the dominant model (OR, 0.66; 95% CI, 0.46–0.95), while another SNP in RP1 (rs9298506) showed a risk effect on IA in a recessive model (OR, 3.82; 95% CI, 1.84–7.91). No associations were observed among common variants near EDNRA, SOX17, or RBBP8 and IA. CONCLUSION: These data partially confirmed earlier results and showed that variants in CDKN2B-AS1, RP1, and HDAC9 could be genetic susceptibility factors for IA in a Chinese population.


Assuntos
Grupo com Ancestrais do Continente Asiático , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Aneurisma Intracraniano , Modelos Logísticos , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Características da População
17.
Yonsei Medical Journal ; : 659-666, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762094

RESUMO

PURPOSE: To investigate associations for polymorphisms in β-carotene 9′,10′-oxygenase (BCO2, rs10431036 and rs11214109), proprotein convertase subtilisin kexin type 9 (PCSK9, rs11583680), and tribbles pseudokinase 1 (TRIB1, rs17321515 and rs2954029), as well as lifestyle factors, with ischemic stroke (IS). MATERIALS AND METHODS: This nested case-control study included 161 patients with IS and 483 matched control individuals. We collected medical reports, lifestyle details, and blood samples from individuals and used the PCR-ligase detection reaction method to genotype single nucleotide polymorphisms (SNPs). RESULTS: The GA+AA genotype of rs10431036 (p<0.001) and rs17321515 (p=0.003), the CT+TT genotype of rs11214109 (p=0.005), and the TA+AA genotype of rs2954029 (p=0.006) in dominant models increased the risk of IS. In additive models, the GG genotype of rs17321515 (p=0.005) and the TT genotype of rs2954029 (p=0.008) increased the risk of IS. Adequate intake of fruits/vegetables reduced the risk of IS (p=0.005). Although there was no interaction between genes and fruits/vegetables, people with inadequate intake of fruits/vegetables who carried a risk genotype had a higher risk of IS than those only having inadequate fruits/vegetables intake or those only carrying a risk genotype. Also, the haplotypes AC, AT, and GT (comprising rs10431036 and rs11214109) and GT (comprising rs2954029 and rs17321515) were found to be associated with an increased risk of IS (p<0.05). CONCLUSION: Polymorphisms in BCO2 and TRIB1 and fruits/vegetables intake were associated with IS. These results provide the theoretical basis for gene screening to prevent chronic cerebrovascular diseases.


Assuntos
Estudos de Casos e Controles , Transtornos Cerebrovasculares , Genótipo , Haplótipos , Humanos , Estilo de Vida , Programas de Rastreamento , Métodos , Polimorfismo de Nucleotídeo Único , Pró-Proteína Convertases , Acidente Vascular Cerebral , Subtilisina
18.
Yonsei Medical Journal ; : 700-703, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762089

RESUMO

Congenital analbuminemia (CAA) is an autosomal recessive disease characterized by extremely low serum levels of albumin. CAA is caused by various homozygous or heterozygous mutations of the ALB gene. Patients often exhibit no clinical symptoms, aside from rare accompanying conditions, such as fatigue, ankle edema, and hypotension. This case report describes the case of a 28-year-old asymptomatic Korean male referred to our center with hypocalcemia, vitamin D deficiency, and hypoalbuminemia who was diagnosed with CAA. To determine the cause of hypoalbuminemia in the patient, laboratory tests, radiological examination, and DNA sequencing were performed. The patient was confirmed to not exhibit any other clinical conditions that can induce hypoalbuminemia and was diagnosed with CAA using DNA sequencing. The present case of CAA is the first to be reported in Korea.


Assuntos
Adulto , Tornozelo , Edema , Fadiga , Humanos , Hipoalbuminemia , Hipocalcemia , Hipotensão , Coreia (Geográfico) , Masculino , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Deficiência de Vitamina D
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772121

RESUMO

OBJECTIVE@#To investigate the association of genetic polymorphisms of norepinephrine metabolizing enzymes with postpartum depression and analyze the risk factors for postpartum depression in women following cesarean section.@*METHODS@#A total of 591 Chinese woman of Han Nationality undergoing caesarean section were enrolled in this study. The diagnosis of postpartum depression was established for an Edinburgh Postnatal Depression Scale (EPDS) score ≥9. For all the women without antepartum depression, the genotypes of catechol-O-methyltransferase (COMT; at 5 sites including rs2020917 and rs737865) and monoamine oxidase A (rs6323) were determined using Sequenom Mass Array single nucleotide polymorphism (SNP) analysis. We analyzed the contribution of the genetic factors (SNPs, linkage disequilibrium and haplotype) to postpartum depression and performed logistic regression analysis to identify all the potential risk factors for postpartum depression and define the interactions between the genetic and environmental factors.@*RESULTS@#The incidence of postpartum depression was 18.1% in this cohort. Univariate analysis suggested that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype) were significantly correlated with the occurrence of postpartum depression ( < 0.05). Logistic regression analysis showed that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype), severe stress during pregnancy, and domestic violence were the risk factors for postpartum depression ( < 0.05); no obvious interaction was found between the genetic polymorphisms and the environmental factors in the occurrence of postpartum depression.@*CONCLUSIONS@#The rs2020917TT and rs737865GG genotypes of COMT, stress in pregnancy, and domestic violence are the risk factors for postpartum depression.


Assuntos
Catecol O-Metiltransferase , Genética , Cesárea , Depressão Pós-Parto , Diagnóstico , Genética , Violência Doméstica , Psicologia , Feminino , Interação Gene-Ambiente , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Monoaminoxidase , Genética , Norepinefrina , Metabolismo , Polimorfismo de Nucleotídeo Único , Complicações Pós-Operatórias , Diagnóstico , Genética , Gravidez , Complicações na Gravidez , Psicologia , Fatores de Risco , Estresse Psicológico
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772027

RESUMO

OBJECTIVE@#To assess the association of single nucleotide polymorphisms (SNPs) of dual specificity phosphatase 9 (DUSP9) gene rs5945326 locus with gestational diabetes mellitus (GDM).@*METHODS@#Genotypes for the rs5945326 locus were determined for 206 pregnant women with GDM (GDM group) and 189 unaffected pregnant women (control group). Allelic and genotypic frequencies of the GDM and control groups were compared. For individuals with various genotypes, the level of blood glucose, serum lipids, and body mass index (BMI) were also compared.@*RESULTS@#The frequencies of AA, AG and GG genotypes for the GDM group were 32.2%, 52.2% and 15.6%, respectively, and 41.2%, 43.9% and 15.0%, for the control group, respectively. No significant difference was detected in the distribution of above genotypes between the two groups (chi-square=3.601, P=0.165). The frequencies of alleles A and G were 58.3% and 41.7% in the GDM group, and 63.1% and 36.9% in the control group, respectively. No significant difference was detected between the two groups too (chi-square=1.894, P=0.188). The high density lipoprotein (HDL) levels of the GG genotype [(2.34×0.61) mmol/L] was significantly higher than that of the AG+AA genotype [(2.06×0.56) mmol/L] (t=2.993, P=0.003). No significant difference was detected in other clinical indexes between the two groups (P> 0.05).@*CONCLUSION@#The SNP rs5945326 in DUSP9 gene may be not associated with the risk of GDM. However, there are correlated with HDL levels.


Assuntos
Alelos , Diabetes Gestacional , Genética , Fosfatases de Especificidade Dupla , Genética , Feminino , Frequência do Gene , Genótipo , Humanos , Fosfatases da Proteína Quinase Ativada por Mitógeno , Genética , Polimorfismo de Nucleotídeo Único , Gravidez
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