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1.
Arch Virol ; 165(3): 691-702, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32016546

RESUMEN

Here, we present the results of a study in which 639 samples obtained between October 2018 and April 2019 from patients with symptoms of acute gastroenteritis were tested for the presence of a rotavirus infection. The antigen of group A rotavirus was detected in 160 samples (25% of those tested). To study the genetic diversity of group A rotavirus, RNA was isolated from the samples, and polymerase chain reaction combined with reverse transcription (RT-PCR) with primers specific for the VP4, VP6, and VP7 genes of group A rotaviruses was performed. At least one fragment of the group A rotavirus genome was found in 101 samples (15.8%). These fragments were sequenced, and their G and P genotypes-as well as their combinations-were determined. The predominant G genotypes were G9 (35.8% of all genotyped samples) and G4 (28.4%), but the rare G12 genotype was also found (3.0%). The dominant P genotype was P[8]. The spectrum of certain G/P combinations of genotypes included seven variants. The most common variants were G9P[8] (37.2%) and G4P[8] (30.2%).


Asunto(s)
Variación Genética , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , Rotavirus/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Niño , Preescolar , Genotipo , Humanos , Lactante , Persona de Mediana Edad , Moscú , Filogenia , Proteínas Virales/química , Proteínas Virales/genética , Proteínas Virales/metabolismo , Adulto Joven
2.
Mikrobiyol Bul ; 54(1): 144-153, 2020 Jan.
Artículo en Turco | MEDLINE | ID: mdl-32050885

RESUMEN

Avian chlamydiosis, is a highly contagious, systemic disease occuring in domestic and wild birds. Chlamydia psittaci, the causative agent of the disease, is a gram-negative bacterium in the Chlamydiaceae family that can only live within the cell. The agent can be transmitted directly to humans by contact with infected animals or feces of infected animals. It can also be transmitted by inhalation of fecal dust. Since the disease has a zoonotic character, it is also important in terms of public health. By using the monoclonal antibodies against cell wall proteins (OMP) of C.psittaci, six (A-F) and two (WC and M56) serotypes were determined in mammals. The aim of this study was to investigate and genotype the presence of C.psittaci ompA gene in domestic pigeon feces grown in family management style in ten different districts in Ankara in winter and summer seasons. Within the scope of the study, 100 pigeon stool samples were collected from birdhouses in 10 different districts of Ankara (Beypazari, Haymana, Kizilcahamam, Cubuk, Pursaklar, Bala, Cankaya, Polatli, Golbasi and city center) in two different seasons. DNA extraction from fecal samples was performed by classical methods. The presence of the agent in the extracted DNA samples was investigated by polymerase chain reaction (PCR) analysis of the ompA gene. Two-way sequence analysis of the ompA gene was performed with the primers used in the study from the target DNA products amplified by PCR. The results of sequence analysis were compared with the international database and serotyping/genotyping was performed. In the study, C.psittaci ompA gene was detected in 6 (6%) samples of 100 pigeon stool samples. Among these positive samples, two were from Bala (one sample from winter, one sample from summer), two were from Haymana (one sample from winter, one sample from summer) and two were from Golbasi (one sample from winter, one sample from summer); where the same agent was isolated in the same aviaries in different seasons. In this study, no difference was found between the presence of C.psittaci in pigeon droppings and season. In addition when the sequence analysis of the isolated samples were compared with the World database; all isolates were found to be 100% genotype B and 99% genotype E. In this study, the sequence analysis of the ompA gene of C.psittaci from domestic pigeon feces was determined for the first time in Turkey. Although the presence of C.psittaci in domestic pigeons is low, it is a zoonotic bacterium and is important for the public health.


Asunto(s)
Proteínas de la Membrana Bacteriana Externa , Enfermedades de las Aves , Chlamydophila psittaci , Columbidae , Heces , Psitacosis , Animales , Proteínas de la Membrana Bacteriana Externa/genética , Enfermedades de las Aves/microbiología , Chlamydophila psittaci/genética , Columbidae/microbiología , Heces/microbiología , Genotipo , Psitacosis/microbiología , Turquia
3.
J Assoc Physicians India ; 68(2): 35-38, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32009360

RESUMEN

Abstract: The interplay between Hepatitis C virus (HCV) and immune system, especially T lymphocytes play a major role in the clearance of virus and in development of liver cell injury resulting in replacement of healthy tissue with fibrous scar tissue. Objectives: To evaluate the association of CD4/CD8 ratio with viral load and genotype of HCV and to evaluate the correlation of CD4/CD8 ratio and CD4 and CD8 cell counts with liver function tests in HCV infected patients. Methods: Forty patients of Chronic Hepatitis C infection were enrolled for study. Immunophenotyping by flowcytometry for measurement of CD4 and CD8 T cell counts was used and the percentages of cells expressing CD4 and CD8 were estimated per lymphocyte population. HCV viral load quantitative was done by Roche Taqman Method. Results: The CD4/CD8 ratio was not found to have any significant correlation with HCV viral load. However, it showed a significant difference in the two HCV genotypes, the ratio being higher in genotype 3 than in genotype 1. It showed no significant correlation with liver function tests except serum albumin which had significant positive correlation with CD4/CD8 ratio. The ratio was also found to be significantly decreased in patients with cirrhosis of liver. Conclusion: Hepatitis C virus genotype but not viral load influences the immune response to HCV infection. The CD4/CD8 ratio significantly decreases in patients with liver cirrhosis than in normal and fatty liver.


Asunto(s)
Hepatitis C Crónica/epidemiología , Cirrosis Hepática/epidemiología , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Genotipo , Hepatitis C , Hepatitis C Crónica/virología , Humanos , Carga Viral
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 40-50, 2020 Feb.
Artículo en Chino | MEDLINE | ID: mdl-32027251

RESUMEN

OBJECTIVE: To investigate the correlation of single nucleotide polymorphisms (SNP) in arachidonate 5-lipoxygenase gene (ALOX5) rs2029253, rs2228064 and rs2228065 sites, 5-lipoxygenase activating protein gene (ALOX5AP) rs10507391, rs4769874 sites with the risk for genesis of adult myeloid leukemia. METHODS: By the approval from the hospital ethics committee and the informed consent of participants. 150 patients with myeloid leukemia (ML) as ML group and 134 healthy people as the control group were selected. The genomic DNA was extracted from the samples. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with directly sequencing, PCR-amplified products were applied to test the polymorphism of 5 sites in ALOX5 and ALOX5AP gene. RESULTS: A allele frequencies of ALOX5 gene rs2029253 site in the ML group and the control group were 43.0% and 34.3%, respectively. And the G allele frequencies in the ML group and the control group were 57.0% and 65.7%, respectively. The genotype distributions of AA, AG and GG in ALOX5 gene rs2029253 site in the ML group were 32.2%, 21.5% and 46.3% respectively. That in the control group were 15.7%, 37.3% and 47.0% respectively. The genotype AA and A allele frequency of ALOX5 gene rs2029253 site were linked with the increased risk of myeloid leukemia (OR=2.26, 95% CI: 1.43-4.56, P<0.05; OR=1.44, 95% CI: 1.02-2.03, P<0.05). And the genotype AG and allele G reduced the susceptibility to myeloid leukemia (OR=0.46, 95% CI: 0.27-0.78, P<0.01; OR=0.69, 95% CI: 0.50-0.98, P<0.05), however, the polymorphisms of ALOX5 gene rs2228064 and rs2228065 site not correlated with the risk of myeloid leukemia (P>0.05). The A allele frequency of ALOX5AP gene rs10507391 site in the ML group and the control group were 30.7% and 36.2% respectirely. The genotype distribution rates of AA, AT and TT in ALOX5AP gene rs10507391 site in the ML group was 1.3%, 58.7% and 40.0% respectively, that in the control group were 9.7%, 53.0% and 37.3% respectively. The genotype AA of ALOX5AP gene rs10507391 site correlated with the decreased risk of myeloid leukemia (OR=0.13, 95% CI: 0.03-0.57, P<0.05), but the polymorphism of ALOX5AP gene rs4769874 site not correlated with the risk of myeloid leukemia (P>0.05). CONCLUSION: The genotype AA, AG and allele A, G of ALOX5 rs2029253, as well as ALOX5AP rs10507391 may be correlate with the susceptibility to myeloid leukemia.


Asunto(s)
Proteínas Activadoras de la 5-Lipooxigenasa/genética , Araquidonato 5-Lipooxigenasa/genética , Leucemia Mieloide , Adulto , Estudios de Casos y Controles , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Leucemia Mieloide/genética , Polimorfismo de Nucleótido Simple , Factores de Riesgo
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 296-299, 2020 Feb.
Artículo en Chino | MEDLINE | ID: mdl-32027292

RESUMEN

OBJECTIVE: To establise the bank of platelet donors with the human platelet antigen (HPA) 1-6, 15 genes so as to provide the HPA-matched platelets for the patients. METHODS: The HPA genotyping of platelets donors and patients with platelet antibody positive confirmed by sercening was performed by using the SSP-PCR; the efficacy of transfusing the HPA-matched platelets for 37 cases platelet antibody positive was analyzed. RESULTS: The most common genotype in platelet donors were HPA-1a/1a-2a/2a-3a/3b-4a/4a-5a/5a-6a/6a-15a/15b, followed by HPA-1a/1a-2a/2a-3a/3a-4a/4a-5a/5a-6a/6a-15a/15b; the most common genotype in 53 cases of platelet antibody positive confirened by screening were HPA-1a/1a-2a/2a-3a/3b-4a/4a-5a/5a-6a/6a-15a/15b. Among 37 patients with platelet antibody positive confirened by screeming, 28 showed that the transfusion of HPA-matched platelets was effective with statistically significant difference in comparison with random transfusion group. The HPA-3, HPA-15 were the main factors leading to polymorphisms. CONCLUSION: HPA-3 and HPA-15 are polymorphic, which should be focused on. HPA-matched platelets can improve the efficiency of platelet transfusion, and avoid the waste of blood resources. The genotypes of platelet donors can basically meet the requirements for common genotype transfusion.


Asunto(s)
Plaquetas , Antígenos de Plaqueta Humana , Donantes de Sangre , Frecuencia de los Genes , Genotipo , Humanos , Polimorfismo Genético
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 300-306, 2020 Feb.
Artículo en Chino | MEDLINE | ID: mdl-32027293

RESUMEN

OBJECTIVE: To study the single nucleotide polymorphisms (SNPs) in promoter region of the Jk gene and its allele frequency as well as distribution characteristics in the Chinese Han nationality population. METHODS: 127 blood samples containing 8 Jk(a-b-) and 119 samples (as control) taken randomly from voluntary blood donors of Chinese Han nationality persons in Shenzhen Blood Center were collected. The Kidd phenotypes were identified by using the serologic test and urea hemolysis test; the Jk promoter, exon 1-11 region and respective flanking area were amplified and sequenced, then the sequence information was analyzed. RESULTS: 8 Jk(a-b-) samples all carried JkB/JkB allele which belongs to 2 kind of Jknull genotypes commonly observed in Chinese Han nationality population. 6 IVS5-1g>a and 2 896G>A were found in 8 Jk(a-b-) samples. Besides, all Jk(a-b-) samples were homozygous for JkB/JkB allele. Three SNPs-110(rs900974), -160(rs1484877) and -258(rs1484878) in promoter region of the Jk gene were found and sequenceds calculation of allele and genotype frequencies showed that the result accorded with Hardy-Weinberg equilibrium, indicating that the population in this study possesses representative characteristics of the Chinese Han nationality population. CONCLUSION: The polymorphism of the Jk gene occurs in promoter region. This study calculates the allele frequencies of three SNPs-110(rs900974), -160(rs1484877) and -258(rs1484878) in promoter region of the Jk gene, and shows their distribution characteristics in distinct Kidd phenotypes. These findings provide the basic foundation for further population genetics research.


Asunto(s)
Polimorfismo de Nucleótido Simple , Alelos , Antígenos de Grupos Sanguíneos , China , Frecuencia de los Genes , Genotipo , Humanos , Sistema del Grupo Sanguíneo de Kidd , Regiones Promotoras Genéticas
7.
Medicine (Baltimore) ; 99(3): e18722, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32011449

RESUMEN

The prevalence of risk factors of chronic kidney disease in Saudi Arabia has augmented an already serious public health problem, therefore, determination of genetic variants associated with the risk of the disease presents potential screening tools that help reducing the incidence rates and promote effective disease management.The aim of the present study is to determine the association of UMOD and MYH9 genetic variants with the risk of non-diabetic end-stage renal disease (ESRD) in the Saudi population.Two single nucleotide polymorphisms (SNP), rs12917707 in gene UMOD and rs4821480 in gene MYH9 were genotyped in 154 non-diabetic ESRD Saudi patients and 123 age-matched healthy controls using Primers and Polymerase chain reaction conditions (PCR), Sanger sequencing, and TaqMan Pre-designed SNP Genotyping Assay. The association of these genetic variants with the risk of the disease and other renal function determinants was assessed using statistical tools such as logistic regression and One-way Analysis of Variance tests.The genotypic frequency of the two SNPs showed no deviation from Hardy-Weinberg equilibrium, the minor allele frequency of UMOD SNP was 0.13 and MYH9 SNP was 0.08. rs4821480 in MYH9 was significantly associated with the risk of non-diabetic ESRD (OR = 3.86; 95%CI: 1.38-10.82, P value .010), while, rs12917707 showed lack of significant association with the disease, P value .380. and neither of the 2 SNPs showed any association with the renal function determinants, serum albumin, and alkaline phosphatase enzyme.


Asunto(s)
Fallo Renal Crónico/genética , Cadenas Pesadas de Miosina/genética , Uromodulina/genética , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Estudios Retrospectivos , Arabia Saudita/epidemiología
8.
Chin J Physiol ; 63(1): 43-49, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32056986

RESUMEN

The DNA repair capacity plays a critical role in maintaining the genomic stability and gatekeeping for individual cancer risk. In this study, we aim at evaluation the role of the Asp148Glu (rs1130409) variant at apurinic/apyrimidinic endonuclease (APE) gene in renal cell carcinoma (RCC) risk and the contribution of different genotypes to its transcriptional mRNA levels. In the case-control study, 92 RCC patients and 580 cancer-free patients matched by age and gender were recruited. The apurinic/APE genotyping work was conducted with typical restriction fragment length polymorphism methodology after polymerase chain reaction. At the meanwhile, thirty renal tissue samples with variant genotypes were examined for their apurinic/APE mRNA and protein expressions by real-time quantitative reverse transcription method and Western blotting. The results showed that compared with the wild-type TT genotype, the people with TG and GG genotypes of apurinic/APE Asp148Glu had 0.88- and 1.09-fold risk of RCC, respectively. We have also examined the in vivo transcriptional (RNA) and translational (protein) levels with renal tissues of various apurinic/APE Asp148Glu genotypes, revealing that the apurinic/APE mRNA and protein were of similar levels among people of TT, TG, or GG genotypes. There was no joint gene-environment effect of apurinic/APE Asp148Glu genotype and smoking habit on RCC risk. The evidence indicated that apurinic/APE Asp148Glu genotypic variants did not alter its mRNA and protein expression among RCC patients. The genotype of apurinic/APE Asp148Glu may not serve as a proper predictive marker for RCC risk in Taiwan.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Estudios de Casos y Controles , Reparación del ADN , ADN-(Sitio Apurínico o Apirimidínico) Liasa , Endonucleasas , Genotipo , Humanos , Fenotipo , Taiwán
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(2): 141-145, 2020 Feb.
Artículo en Chino | MEDLINE | ID: mdl-32051081

RESUMEN

OBJECTIVE: To study the association of single nucleotide polymorphisms (SNPs) of interleukin-23 receptor (IL-23R) rs10889677, interleukin-17A (IL-17A) rs227591, and interleukin-17F (IL-17F) rs763780 with necrotizing enterocolitis (NEC) in Chinese Han preterm infants. METHODS: A total of 100 Chinese Han preterm infants with NEC who were admitted to the neonatal intensive care unit from January 2017 to January 2019 were prospectively enrolled. Of the 100 preterm infants, 63 had stage II NEC and 37 had stage III NEC. A total of 100 preterm infants, matched for age and sex, were selected as the control group. PCR and Sanger sequencing were used to determine the SNPs of rs10889677, rs2275913, and rs763780. An unconditional logistic regression analysis was used to investigate the association of SNPs with NEC susceptibility and severity. RESULTS: The genotype and allele frequencies of rs10889677 and rs2275913 had no influence on the development of NEC (P>0.05). The genotype of rs763780 had no influence on the development of NEC (P>0.05), but the risk of NEC in the infants carrying C allele was 1.652 times that in those carrying T allele (95%CI: 1.052-2.695, P<0.05). The risk of NEC in the infants carrying TC+CC genotype was 1.856 times that in those carrying TT genotype (95%CI: 1.045-3.201, P<0.05). The risk of stage III NEC in the infants carrying TC+CC genotype was 2.965 times that in those carrying TT genotype (95%CI: 1.052-6.330, P<0.05). The risk of stage III NEC in the infants carrying C allele was 2.363 times that in those carrying T allele (95%CI: 1.034-4.093, P<0.05). CONCLUSIONS: The SNPs of IL-23R rs10889677 and IL-17A rs2275913 are not associated with the susceptibility to NEC in Chinese Han preterm infants, while TC+CC genotype and C allele of IL-17F rs763780 are associated with the susceptibility to NEC and the severity of NEC.


Asunto(s)
Enterocolitis Necrotizante , Interleucina-17/genética , Polimorfismo de Nucleótido Simple , Receptores de Interleucina/genética , Grupo de Ascendencia Continental Asiática , Estudios de Casos y Controles , Enterocolitis Necrotizante/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Recién Nacido , Recien Nacido Prematuro
10.
Expert Opin Drug Metab Toxicol ; 16(1): 1-9, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31914334

RESUMEN

Background: Warfarin acts in heart valve replacement patients to minimize thromboembolic complications. We investigated whether patients can be distinguished based on their genotypes to efficiently and safely administer warfarin therapy after heart valve replacements.Research design and methods: A retrospective analysis was conducted in patients with warfarin therapy who underwent elective heart valve replacements between January 2013 and September 2018. The patients were divided into normal, sensitive, and highly sensitive bins based on their CYP2C9 and VKORC1 genotypes. The primary endpoints were over-anticoagulation and overt bleeding.Results: 375 patients were enrolled, with 65 classified as normal, 281 as sensitive, and 29 as highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders spent more time on over-anticoagulation in the first 28 (P < 0.001) and 90 (P = 0.001) days; experienced more frequent bleeding events in the first 28 days (P = 0.029; OR, 2.18; 95% CI, 1.15-4.13); required lower warfarin doses to obtain stable INR (P < 0.001); had higher warfarin sensitivity indices (P < 0.001).Conclusion: Predicting evidence have been obtained with CYP2C9 and VKORC1 genotypes in identifying heart valve replacement patients with higher efficient sensitivity and with a higher risk of bleeding and over-anticoagulation.


Asunto(s)
Anticoagulantes/administración & dosificación , Citocromo P-450 CYP2C9/genética , Hemorragia/inducido químicamente , Vitamina K Epóxido Reductasas/genética , Warfarina/administración & dosificación , Adulto , Anciano , Anticoagulantes/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Genotipo , Implantación de Prótesis de Válvulas Cardíacas/métodos , Hemorragia/epidemiología , Hemorragia/genética , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tromboembolia/prevención & control , Warfarina/efectos adversos
11.
N Engl J Med ; 382(5): 437-445, 2020 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-31995689

RESUMEN

BACKGROUND: Cytomegalovirus (CMV) can cause severe disease in children and adults with a variety of inherited or acquired T-cell immunodeficiencies, who are prone to multiple infections. It can also rarely cause disease in otherwise healthy persons. The pathogenesis of idiopathic CMV disease is unknown. Inbred mice that lack the gene encoding nitric oxide synthase 2 (Nos2) are susceptible to the related murine CMV infection. METHODS: We studied a previously healthy 51-year-old man from Iran who after acute CMV infection had an onset of progressive CMV disease that led to his death 29 months later. We hypothesized that the patient may have had a novel type of inborn error of immunity. Thus, we performed whole-exome sequencing and tested candidate mutant alleles experimentally. RESULTS: We found a homozygous frameshift mutation in NOS2 encoding a truncated NOS2 protein that did not produce nitric oxide, which determined that the patient had autosomal recessive NOS2 deficiency. Moreover, all NOS2 variants that we found in homozygosity in public databases encoded functional proteins, as did all other variants with an allele frequency greater than 0.001. CONCLUSIONS: These findings suggest that inherited NOS2 deficiency was clinically silent in this patient until lethal infection with CMV. Moreover, NOS2 appeared to be redundant for control of other pathogens in this patient. (Funded by the National Center for Advancing Translational Sciences and others.).


Asunto(s)
Infecciones por Citomegalovirus , Mutación del Sistema de Lectura , Óxido Nítrico Sintasa de Tipo II/deficiencia , Resultado Fatal , Femenino , Genotipo , Homocigoto , Humanos , Mutación con Pérdida de Función , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Linaje , Secuenciación del Exoma Completo
12.
Zhonghua Yi Xue Za Zhi ; 100(2): 136-140, 2020 Jan 14.
Artículo en Chino | MEDLINE | ID: mdl-31937054

RESUMEN

Objective: Tuberous sclerosis complex (TSC) is a multi-system disease with TSC1 and TSC2 genes as the pathogenic genes. The purpose of our study was to analyze the gene mutation in patients with TSC with epilepsy as the main clinical manifestation. The relationship between genotype and phenotype, scalp EEG in patients was analyzed. Methods: The peripheral blood was extracted from 43 patients and their families. TSC gene was detected by second-generation sequencing. Long-term video EEG monitoring and MRI examination were performed to determine the onset area, seizure type and location of nodules. Results: 39 patients had TSC gene mutation, 4 patients did not detect the gene mutation.11 had TSC1 mutations and 28 had TSC2 mutations. 22 mutations were de novo. Patients with TSC2 mutations had earlier seizure and more nodules than patients with TSC1 mutations, but no significant difference in intelligence and spasm were observed. 28 patients had focal origin of scalp EEG, of which 85.7% of TSC2 mutations patients had focal origin. Conclusions: Patients of TSC2 mutations always has an early onset age. Although MRI shows multiple nodules, the onset of EEG is mainly focal origin.


Asunto(s)
Esclerosis Tuberosa , Análisis Mutacional de ADN , Electroencefalografía , Genotipo , Humanos , Mutación , Fenotipo , Proteína 1 del Complejo de la Esclerosis Tuberosa , Proteína 2 del Complejo de la Esclerosis Tuberosa
13.
Medicine (Baltimore) ; 99(2): e18725, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31914088

RESUMEN

The NOTCH signaling pathway plays a crucial role in cell phenotype and transformation. Single nucleotide polymorphisms (SNPs) may regulate gene expression to trigger bladder cancer susceptibility. Here, we aimed to explore the relationships between genetic variants in the NOTCH pathway and bladder cancer progression.We screened SNPs located in NOTCH pathway genes using the 1000 Genomes Project dataset (CHB). A case-control cohort study including 580 bladder cancer cases and 1101 controls was conducted to genotype the candidate SNPs. The expression quantitative trait locus (eQTL) and bioinformatics analyses were performed to explore the biological function of the SNPs' host gene and their relationship. Kaplan-Meier analysis was performed to assess the association between host gene expression and bladder cancer patient prognosis.The rs7944701 in the intron of mastermind-like 2 (MAML2) had the strongest signal and was related to bladder cancer risk (OR = 1.329, 95% CI = 1.115-1.583, P = .001). eQTL analysis showed that rs7944701 with a C allele was negatively associated with mastermind-like 2 (MAML2) expression (TT versus TC/CC). Bioinformatics analysis indicated that MAML2expression was lower in bladder cancer tissues than in non-tumor tissues (P = 5.46 × 10). Additionally, bladder cancer patients with high MAML2 expression had a significantly poorer prognosis (HR = 1.53, 95% CI = 1.29-1.82, P = .010).The rs7944701 in MAML2 was strongly associated with bladder cancer susceptibility in a Chinese population. This genetic variant and its host gene could be a potential novel biomarker for individuals suffering from bladder cancer.


Asunto(s)
Transactivadores/genética , Neoplasias de la Vejiga Urinaria/genética , China , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Intrones , Estimación de Kaplan-Meier , Masculino , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Transducción de Señal
14.
Expert Opin Pharmacother ; 21(3): 261-273, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31914336

RESUMEN

Introduction: Hepatitis C virus (HCV) is estimated to infect approximately 70 million people worldwide. If left untreated, chronic infection can progress to cirrhosis, liver failure or hepatocellular carcinoma. The advent of new direct-acting antivirals (DAA) has revolutionized patients' chances of treatment and viral elimination. Currently, several DAA options are available on the market.Areas covered: This review focuses on the pharmacokinetics, efficacy, tolerability and safety profile of DCV-TRIO, a twice-daily fixed-dose combination of daclatasvir, asunaprevir and beclabuvir approved in Japan for the treatment of genotype 1 HCV infection.Expert opinion: The DCV-TRIO combination achieved good response rates in genotype 1 patients (SVR12 ≥ 95% in naïve subtype 1b), independently from IL28B genotype, cirrhotic status and prior interferon exposure. On the other hand, unsatisfying response rates were reported in DAA-experienced patients and the risk of RAS selection should not be underestimated. Moreover, DCV-TRIO lacks differentiation from its earlier-launched DAA rivals, presents an inconvenient twice-daily dosing schedule and is not recommended in patients with advanced liver and kidney disease. All these drawbacks considerably limit its effective commercial potential. However, it can be a therapeutic option against HCV in tailored approaches according to the needs of different markets across the world.Abbreviations AE: adverse event; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ASV: asunaprevir; AUC: area under the curve; BCRP: Breast Cancer Resistance Protein; BCV: boceprevir; BID: bis in die; CI: confidence intervals; CLcr: creatinine clearance; DAA: direct acting antivirals; DCV: daclatasvir; EC50: Half maximal effective concentration; GT: genotype; HCV: Hepatitis C virus; IFN: Interferon; NHL: non-Hodgkin lymphoma; OATP: Organic anion transporting polypeptides; OR: odds ratio; P-gp: P-glycoprotein; PK: pharmacokinetics; QD: quo die; RAS: resistance-associated substitutions; SVR: sustained virological response; USD: Unites States dollar.


Asunto(s)
Benzazepinas/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Imidazoles/administración & dosificación , Indoles/administración & dosificación , Isoquinolinas/administración & dosificación , Sulfonamidas/administración & dosificación , Antivirales/uso terapéutico , Combinación de Medicamentos , Genotipo , Hepacivirus/efectos de los fármacos , Humanos , Cirrosis Hepática/prevención & control , Respuesta Virológica Sostenida , Comprimidos , Resultado del Tratamiento
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 33-36, 2020 Jan 10.
Artículo en Chino | MEDLINE | ID: mdl-31922592

RESUMEN

OBJECTIVE: To explore hematological and genotypic characteristics of patients with hemoglobin E (Hb E) disorders from Yunnan Province. METHODS: One hundred individuals with Hb E disorders indicated by high performance liquid chromatography (HPLC) were subjected to genetic testing through multiple gap-PCR and reverse dot-blotting analysis. RESULTS: All patients were found to harbor a mutation to the 26th codon of the ß -globin chain (HBB: c.79G>A). Ninety patients were heterozygotes, and 10 co-inherited c.79G>A and an α -thalassemia mutation (7 α α /-α3.7, 2 α α /--SEA and 1 -α 3.7/-α3.7). Hematological characteristics of the heterozygotes were: Hb A2 (26.02±3.64)%, Hb F(1.35±1.25)%, MCV(78.83±4.68) fl, MCH(26±1.54) pg, MCHC (329.65±10.73) g/L, HGB (141.08±16.53) g/L, while that of the co-inherited cases was decided by the type of α -thalassemia mutation. CONCLUSION: Hb E can be effectively detected by HPLC. The type of α -thalassemia mutations will determine hematological features of co-inherited cases. Hb E disorders may be missed by relying only on routine blood test upon prenatal screening.


Asunto(s)
Hemoglobina E , Talasemia alfa , China , Femenino , Genotipo , Hemoglobina E/genética , Humanos , Mutación , Embarazo , Talasemia alfa/genética , Globinas beta/genética
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 71-74, 2020 Jan 10.
Artículo en Chino | MEDLINE | ID: mdl-31922602

RESUMEN

OBJECTIVE: To explore the molecular basis for an individual with ABO subtype. METHODS: The ABO phenotype of the proband was determined by convention serological testing. Exons 6 and 7 of the ABO gene were subjected to PCR amplification and bi-directional Sanger sequencing. Haplotypes for exons 6 and 7 of the proband was determined using an ABO haplotype-specific amplification and sequencing technique. RESULTS: Red blood cells of the proband showed a 4+ agglutination strength with anti-A or anti-H, no agglutination reaction with anti-A1, and a 3+ agglutination strength with anti-B. His serum had no reaction with standard A cells, O cells or self cells, but was weakly reactive with B cells at 4℃. The proband was assigned as an ABO subtype based on his serological features. Bi-directional sequencing of the ABO gene revealed heterozygosity of 261 G/del, 297AG, 526CG, 657CT, 703GA, 803GC and 930GA, and homozygosity of 796CC in the proband. Haplotype-specific amplification and sequencing showed that one of his alleles was ABO*O.01.01, and another contained a c.796A>C variation compared with the ABO*B.01 allele, which led to replacement of methionine by leucine at position 266. Searching the ABO allele database of International Society of Blood Transfusion suggested the variation to be a novel one. CONCLUSION: The c.796A>C variation in the ABO*B.01 allele probably underlies the CisAB subtype. Accurate identification of the ABO subtype requires combined use of serological method and genetic testing.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Variación Genética , Sistema del Grupo Sanguíneo ABO/genética , Alelos , Exones , Genotipo , Humanos , Masculino , Fenotipo , Análisis de Secuencia de ADN
17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(1): 75-79, 2020 Jan 10.
Artículo en Chino | MEDLINE | ID: mdl-31922603

RESUMEN

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< 0.05) and the risk for cleft lip with or without cleft palate (CL/P) to 62% (P< 0.05). rs11621316 and rs1057744 are in the same linkage disequilibrium (LD) region with a high degree of linkage (γ 2> 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.


Asunto(s)
Labio Leporino , Fisura del Paladar , Proteína Jagged-2 , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , China , Labio Leporino/genética , Fisura del Paladar/genética , Frecuencia de los Genes , Genotipo , Humanos , Proteína Jagged-2/genética
18.
Anticancer Res ; 40(1): 27-34, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892550

RESUMEN

BACKGROUND/AIM: Even though prostate cancer (PCa) has good prognosis, there is a discrepancy in the risk among ethnic groups, with high morbidity in African American men. Single nucleotide polymorphisms (SNPs) in interleukin 10 (IL-10) have been associated with inflammation and cancer risk. We investigated the association of five SNPs in the IL-10 promoter with clinical features such as Gleason score and smoking. MATERIALS AND METHODS: A total of 413 DNA samples were obtained from a nested case-control study of African American males who were genotyped for 5 SNPs utilizing pyrosequencing. Multiple and binary logistic regression models were applied to analyze the clinical and genotypic data. RESULTS: rs12122923 and rs1800871 were associated with PCa risk. Smoking was also found to increase the risk of PCa by 1.6-fold. rs1800893 was found to be associated with lower grades for prostate cancer. CONCLUSION: IL-10 promoter polymorphisms might be a risk factor for PCa development in smoking subjects and PCa progression.


Asunto(s)
Afroamericanos/genética , Interleucina-10/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Neoplasias de la Próstata/etiología , Fumar/efectos adversos , Anciano , Alelos , Biomarcadores , Estudios de Casos y Controles , Susceptibilidad a Enfermedades , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/patología , Medición de Riesgo , Factores de Riesgo
19.
Zhonghua Er Ke Za Zhi ; 58(1): 35-40, 2020 Jan 02.
Artículo en Chino | MEDLINE | ID: mdl-31905474

RESUMEN

Objective: To investigate the genotype and phenotype of children with KCNA2 gene related developmental and epileptic encephalopathy (DEE). Methods: Clinical data including the manifestations and electroencephalogram of 8 children with KCNA2 variants treated in the Department of Pediatrics, Peking University First Hospital from March 2017 to June 2019 were collected and analyzed retrospectively. Results: Among the 8 epileptic patients with KCNA2 variants, 5 were males and 3 were females. The age of onset was from 1 day to 11 months. The age at last follow-up ranged from 4 months to 86 months. Two variants including c.1214C>T (loss-of-function) and c.1120A>G (gain-and loss-of-function) were identified. The variant of c.1214C>T was found in six patients (case 1-6). For these patients, the age of onset was from 5 to 11 months and they were characterized by multiple seizure types. All had focal seizures and had normal development before seizure onset with developmental regression after seizure onset. The first electroencephalogram showed epileptic discharges in Rolandic region in two, epileptic discharges in Rolandic region combined with generalized discharge in one, generalized discharge with posterior predominance in two (combined with or transferred to Rolandic region during the course) and epileptic discharges in posterior region combined with generalized discharge in one. And in 5 of them the Rolandic discharges developed into epileptic electrical status (ESES) during sleep. All the six patients were still treated with a combination of multiple antiepileptic drugs. Two of them had seizure controlled at 80 months and 68 months, respectively. The variant of c.1120A>G were identified in two of eight patients (case 7 and 8) and they had seizure onset on the 1st day after birth. Their epileptic seizures were frequent and difficult to control. They had remarkably developmental delay and microcephaly since birth. One case (case 8) had a wide forehead. They had frequent seizures up to the last follow-up. In case 7, the early electroencephalogram showed epileptic discharges in temporal region, and interictal electroencephalogram at 3 months of age showed multifocal discharge with posterior and temporal region predominance. In case 8, the early electroencephalogram was normal and electroencephalogram showed burst suppression at 2 months of age, and it developed epileptiform discharge in posterior region at 1 year of age. Conclusions: KCNA2 gene variants can lead to DEE with multiple seizures types. Among them, loss-of-function c.1214C>T is the most common, and these patients have seizure onset at infancy with Rolandic discharges tended to develop into to ESES pattern. The variant of c.1120A>G is a gain-of- and loss-of-function variant, patients with c.1120A>G have seizure onset in neonatal period, the phenotype overlaps with the former but is more severe.


Asunto(s)
Encefalopatías/genética , Epilepsia/diagnóstico , Canal de Potasio Kv.1.2/genética , Convulsiones , Edad de Inicio , Encéfalo/fisiopatología , Encefalopatías/fisiopatología , Niño , Preescolar , Discapacidades del Desarrollo/fisiopatología , Epilepsia/complicaciones , Epilepsia/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Fenotipo , Estudios Retrospectivos
20.
Zhonghua Er Ke Za Zhi ; 58(1): 41-45, 2020 Jan 02.
Artículo en Chino | MEDLINE | ID: mdl-31905475

RESUMEN

Objective: To evaluate the effectiveness of eradication therapy based on Helicobacter pylori (Hp) susceptibility and CYP2C19 genotype in children with refractory Hp infection. Methods: In this prospective observational cohort study, 156 children with Hp refractory to amoxicillin+clarithromycin+omeprazole triple regimen in Baoding Children's Hospital from December 2017 to May 2018 were enrolled. Ninety-two of them underwent Hp culture and CYP2C19 detection. Seventy-five cases with positive Hp culture were defined as culture successful group and were treated according to Hp susceptibility and CYP2C19 genotype. Seventeen cases with negative Hp culture were defined as culture failed group and were treated only based on the results of CYP2C19 genotype. Sixty-four children who did not have Hp culture and CYP2C19 gene testing were defined as the empirical eradication therapy group and were treated with quadruple regimen (amoxicillin+metronidazole+omeprazole+bismuth). Bacterial resistance, CYP2C19 polymorphism and therapeutic effectiveness between the three groups were compared using chi-square test. Results: Among the 75 positive Hp culture results, 72 (96%) were resistant to clarithromycin, 3 (4%) were resistant to metronidazole, 5 (7%) were resistant to levofloxacin, 5 (7%) were resistant to rifampicin, 1 (1%) was resistant to tetracycline, and none was resistant to amoxicillin and furazolidone. The CYP2C19 polymorphism in 92 patients showed that 43 (47%) were extensive metabolizer (EM), 9 (10%) were poor metabolizer (PM), and 40 (43%) were intermediate metabolizer (IM). In terms of the effectiveness, eradication rate in the culture successful group,culture failed group and empirical eradication therapy group were 99% (74/75), 88% (15/17) and 72% (46/64), respectively (χ(2)=21.325, P<0.05). The eradication rate in the culture successful group was significantly higher than that in empirical eradication therapy group (χ(2)=21.005, P<0.05), while there was no difference between empirical eradication therapy group and culture failed group (χ(2)=1.154, P=0.283). Conclusion: Eradication regimen based on bacterial susceptibility and CYP2C19 genotype should be considered in children with refractory Hp infection.


Asunto(s)
Citocromo P-450 CYP2C19/genética , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/genética , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/genética , Omeprazol/uso terapéutico , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Bismuto/uso terapéutico , Niño , Claritromicina/administración & dosificación , Claritromicina/uso terapéutico , Estudios de Cohortes , Resistencia a Medicamentos/genética , Femenino , Genotipo , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Metronidazol/uso terapéutico , Omeprazol/administración & dosificación , Polimorfismo Genético , Estudios Prospectivos , Resultado del Tratamiento
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