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1.
Interdiscip Sci ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817803

RESUMO

In 2002, our research group observed a gene clustering pattern based on the base frequency of A versus T at the second codon position in the genome of Vibrio cholera and found that the functional category distribution of genes in the two clusters was different. With the availability of a large number of sequenced genomes, we performed a systematic investigation of A2-T2 distribution and found that 2694 out of 2764 prokaryotic genomes have an optimal clustering number of two, indicating a consistent pattern. Analysis of the functional categories of the coding genes in each cluster in 1483 prokaryotic genomes indicated, that 99.33% of the genomes exhibited a significant difference (p < 0.01) in function distribution between the two clusters. Specifically, functional category P was overrepresented in the small cluster of 98.65% of genomes, whereas categories J, K, and L were overrepresented in the larger cluster of over 98.52% of genomes. Lineage analysis uncovered that these preferences appear consistently across all phyla. Overall, our work revealed an almost universal clustering pattern based on the relative frequency of A2 versus T2 and its role in functional category preference. These findings will promote the understanding of the rationality of theoretical prediction of functional classes of genes from their nucleotide sequences and how protein function is determined by DNA sequence.

2.
Acad Radiol ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34654623

RESUMO

RATIONALE AND OBJECTIVES: To investigate the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and texture parameters of primary lesions and lymph nodes for predicting pelvic lymph node metastasis in patients with cervical cancer. MATERIALS AND METHODS: A total of 143 patients with cervical cancer confirmed by surgical pathology were analyzed retrospectively and 125 patients were enrolled in primary lesions study, 83 patients and 134 lymph nodes were enrolled in lymph nodes study. Patients and lymph nodes were randomly divided into training group and test group at a ratio of 2: 1. The IVIM-DWI parameters and 3D texture features of primary lesions and lymph nodes of all patients were measured. The least absolute shrinkage and selection operator algorithm, spearman's correlation analysis, independent two-sample t-test and Mann-Whitney U-test were used to select texture parameters. Multivariate Logistic regression analysis and receiver operating characteristic curves were used to model and evaluate diagnostic performances. RESULTS: In primary lesions study, model 1 was constructed by combining f value, original_shape_Sphericity and original_firstorder_Mean of primary lesions. In lymph nodes study, model 2 was constructed by combining short diameter, circular enhancement and rough margin of lymph nodes. Model 3 was constructed by combining ADC, f value and original_glszm_Small Area Emphasis of lymph nodes. The areas under curve of model 1, 2 and 3 in training group and test group were 0.882, 0.798, 0.907 and 0.862, 0.771, 0.937 respectively. CONCLUSION: Models based on IVIM-DWI and texture parameters of primary lesions and lymph nodes both performed well in diagnosing pelvic lymph node metastasis of cervical cancer and were superior to morphological features of lymph nodes. Especially, parameters of lymph nodes showed higher diagnostic efficiency and clinical significance.

3.
J Cell Mol Med ; 25(22): 10494-10503, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34676965

RESUMO

GNE myopathy is a heterogeneous group of ultrarare neuromuscular disorders caused by mutations in the GNE gene. An estimated prevalence of 1~21/1,000,000 leads to a deficiency of data and a lack of availability of samples to conduct clinical research on this neuromuscular disorder. Although GNE, which is the mutated gene responsible for the disease, is well known as the key enzyme in the biosynthesis pathway of sialic acid, the clinicopathological-genetic spectrum of GNE mutant patients is still unclear and expanding. This study presents ten unrelated patients with GNE myopathy, discovering five novel missense mutations. Clinical, electrophysiological, imaging, pathological and genetic data are presented in a retrospective manner. Interestingly, several patients in the cohort were found to have peripheral neuropathy and inflammatory cell infiltration in muscle biopsies, which have seldom been reported. This study, conducted by a neuromuscular centre in China, is the first attempt to highlight these abnormal clinicopathological features and associate them with genetic mutations in GNE myopathy.

4.
Inorg Chem ; 60(11): 7887-7899, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34024091

RESUMO

Three new metal-organic frameworks (MOFs), namely, [Pb7(TTPCA)4Cl2]·3H2O (1), [Pb7(TTPCA)4(DMA)2(HCOO)2]·H2O (2), and [Pb4(TTPCA)3]·3DMF·2H2O·H3O (3), were synthesized by the H3TTPCA ligand [H3TTPCA = 1,1',1″-(1,3,5-triazine-2,4,6-triyl)-tripiperidine-4-carboxylic acid], with lead(II) nitrate under solvothermal conditions. They were characterized by CHN analysis, IR spectroscopy, UV-vis spectroscopy, and single-crystal and powder X-ray diffraction. In addition, their thermogravimetric analysis and fluorescence properties were studied. Compounds 1-3 were 3D MOF structures with different Pbx(COO)y clusters: ([Pb7(COO)12Cl2]), ([Pb7(COO)12]), and [Pb8(COO)18]. Fluorescence detection of compounds 1-3 shows that they can act as excellent sensors of nitrophenols with a low limit of detection and a high quenching constant.

5.
ACS Synth Biol ; 9(11): 3171-3180, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-33048520

RESUMO

Komagataeibacter xylinus has received increasing attention as an important microorganism for the conversion of several carbon sources to bacterial cellulose (BC). However, BC productivity has been impeded by the lack of efficient genetic engineering techniques. In this study, a lambda Red and FLP/FRT-mediated site-specific recombination system was successfully established in Komagataeibacter xylinus. Using this system, the membrane bound gene gcd, a gene that encodes glucose dehydrogenase, was knocked out to reduce the modification of glucose to gluconic acid. The engineered strain could not produce any gluconic acid and presented a decreased bacterial cellulose (BC) production due to its restricted glucose utilization. To address this problem, the gene of glucose facilitator protein (glf; ZMO0366) was introduced into the knockout strain coupled with the overexpression of the endogenous glucokinase gene (glk). The BC yield of the resultant strain increased by 63.63-173.68%, thus reducing the production cost.


Assuntos
Bactérias/genética , Celulose/genética , DNA Nucleotidiltransferases/genética , Gluconacetobacter xylinus/genética , Recombinação Genética/genética , Carbono/metabolismo , Gluconatos/metabolismo , Glucose/genética
6.
Molecules ; 25(18)2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32911616

RESUMO

Based on the ligand H4Salen-8tBu (salen-4), a new dinuclear cobalt complex (salen-4)[Co(III)TFA]2 (salen-4 = 3,5-di-tert-butylsalicylaldehyde-3,3'-diaminobiphenylamine; TFA = trifluoroacetic acid) has been firstly synthesized and characterized. It shows high catalytic activity for the copolymerization of propylene oxide (PO) and carbon dioxide (CO2), yielding regioregular poly(propylene carbonate) (PPC) with little generation of propylene carbonate (PC) by-product. It has been found that (salen-4)[Co(III)TFA]2 shows higher activity at milder conditions, generating a polymer with maximum Mn of 293 kg/mol and a narrow molecular weight distribution PDI of 1.35. The influences of reaction time, CO2 pressure, reaction temperature, nature of the cocatalyst, catalyst dosage and substrate concentration on the molecular weight, yield and selectivity of the polymer were explored in detail. The results showed that the (salen-4)[Co(III)TFA]2/[PPN]TFA catalyst system demonstrated a remarkable TOF as high as 735 h-1. In addition, a hypothetical catalytic reaction mechanism was proposed based on density functional theory (DFT) calculations and the catalytic reaction results of the (salen-4)[Co(III)TFA]2.


Assuntos
Dióxido de Carbono/química , Cobalto/química , Compostos de Epóxi/química , Compostos Organometálicos/química , Cátions/química , Técnicas de Química Sintética , Ligantes , Modelos Químicos , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Polimerização , Teoria Quântica , Análise Espectral , Temperatura
7.
Chem Biodivers ; 17(1): e1900479, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31667925

RESUMO

Chroogomphus rutilus is a rare fungal species that grows under pine trees and is now widely used as a functional food and pharmaceutical product. However, the chemical constituents and biological activities of Chroogomphus rutilus have been relatively limited. The present study aimed at determining the total polyphenols and flavonoids contents, biological activities and main phenolic compounds of Chroogomphus rutilus from different geographical origins at the stipe and pileus. The results suggested that Chroogomphus rutilus polyphenol extracts revealed a higher antioxidant, anti-inflammatory, and cytotoxic activities, and there were significant differences between samples from different locations and regions. Correlation analysis showed that the contents of total polyphenols and flavonoids were significantly correlated with antioxidant and anti-inflammatory activities. However, only the content of total flavonoids was significantly correlated with cytotoxicity, which means that the cytotoxicity of Chroogomphus rutilus polyphenol extracts may be regulated by flavonoids or other compounds. HPLC-DAD analysis revealed that the main phenolic compound was protocatechuic acid, followed by baicalin, p-hydroxyphenylacetic acid and p-hydroxybenzoic acid, but comparing with the pileus extracts, the stipe extracts can be considered as a higher concentration of phenolic compounds. Therefore, antioxidant, anti-inflammatory and cytotoxic activities of Chroogomphus rutilus polyphenol extracts could be due to the identified compounds. This study investigated a deep knowledge about the constituents and activities of Chroogomphus rutilus and provided the reference for its application in food and pharmaceutical.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Basidiomycota/química , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Polifenóis/química , Células RAW 264.7
8.
Inorg Chem ; 58(23): 15898-15908, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31724839

RESUMO

A series of novel metal-organic frameworks were synthesized by using semirigid ligand 1,1',1″-(1,3,5-triazine-2,4,6-triyl)tripiperidine-4-carboxylic acid (H3TTPCA) and lead halide (Cl, Br, or I). The three complexes were characterized by elemental analysis, infrared spectroscopy, ultraviolet-visible spectroscopy, powder X-ray diffraction analysis, and thermogravimetric analysis. X-ray single-crystal diffraction analysis demonstrated that all three complexes were three-dimensional inorganic-organic framework structures with Pb-X2 (X = Cl, Br, or I). However, slight differences in the chemical environment were the focus of the coordinated halogen atoms and the different compositions of metal oxygen clusters: [Pb7(COO)12Cl2], [Pb7(COO)12Br2], and [Pb7(COO)12I2]. Because of the fluorescence of the organic ligand, the three complexes showed similar photoluminescence properties at room temperature, but the intensity of emissions decreased gradually with an increase in the atomic radius of coordinated halogen atoms. Interestingly, in the fluorescence response tests, complexes 1 and 2 displayed an optical signal of fluorescence "turn-on" while complex 3 showed an optical signal of fluorescence "turn-off". Here we aim to provide a possible mechanism to explain these unique and contradictory luminescence results.

9.
Front Microbiol ; 10: 184, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30814982

RESUMO

The in-depth study of viral genomes is of great help in many aspects, especially in the treatment of human diseases caused by viral infections. With the rapid accumulation of viral sequencing data, improved, or alternative gene-finding systems have become necessary to process and mine these data. In this article, we present Vgas, a system combining an ab initio method and a similarity-based method to automatically find viral genes and perform gene function annotation. Vgas was compared with existing programs, such as Prodigal, GeneMarkS, and Glimmer. Through testing 5,705 virus genomes downloaded from RefSeq, Vgas demonstrated its superiority with the highest average precision and recall (both indexes were 1% higher or more than the other programs); particularly for small virus genomes (≤ 10 kb), it showed significantly improved performance (precision was 6% higher, and recall was 2% higher). Moreover, Vgas presents an annotation module to provide functional information for predicted genes based on BLASTp alignment. This characteristic may be specifically useful in some cases. When combining Vgas with GeneMarkS and Prodigal, better prediction results could be obtained than with each of the three individual programs, suggesting that collaborative prediction using several different software programs is an alternative for gene prediction. Vgas is freely available at http://cefg.uestc.cn/vgas/ or http://121.48.162.133/vgas/. We hope that Vgas could be an alternative virus gene finder to annotate new genomes or reannotate existing genome.

10.
Genome Biol Evol ; 10(8): 2072-2085, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30060177

RESUMO

Pandemic cholera is a major concern for public health because of its high mortality and morbidity. Mutation accumulation (MA) experiments were performed on a representative strain of the current cholera pandemic. Although the base-pair substitution mutation rates in Vibrio cholerae (1.24 × 10-10 per site per generation for wild-type lines and 3.29 × 10-8 for mismatch repair deficient lines) are lower than that previously reported in other bacteria using MA analysis, we discovered specific high rates (8.31 × 10-8 site/generation for wild-type lines and 1.82 × 10-6 for mismatch repair deficient lines) of base duplication or deletion driven by large-scale copy number variations (CNVs). These duplication-deletions are located in two pathogenic islands, IMEX and the large integron island. Each element of these islands has discrepant rate in rapid integration and excision, which provides clues to the pandemicity evolution of V. cholerae. These results also suggest that large-scale structural variants such as CNVs can accumulate rapidly during short-term evolution. Mismatch repair deficient lines exhibit a significantly increased mutation rate in the larger chromosome (Chr1) at specific regions, and this pattern is not observed in wild-type lines. We propose that the high frequency of GATC sites in Chr1 improves the efficiency of MMR, resulting in similar rates of mutation in the wild-type condition. In addition, different mutation rates and spectra were observed in the MA lines under distinct growth conditions, including minimal media, rich media and antibiotic treatments.


Assuntos
Pareamento de Bases/genética , Cólera/epidemiologia , Cólera/microbiologia , Deleção de Genes , Duplicação Gênica , Pandemias , Vibrio cholerae/genética , Cromossomos Bacterianos/genética , Meios de Cultura , Período de Replicação do DNA/efeitos dos fármacos , Ilhas Genômicas , Humanos , Taxa de Mutação , Reprodutibilidade dos Testes , Rifampina/farmacologia , Vibrio cholerae/efeitos dos fármacos
11.
BMC Microbiol ; 17(1): 73, 2017 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-28347342

RESUMO

BACKGROUND: Genomic islands (GIs) are genomic regions that reveal evidence of horizontal DNA transfer. They can code for many functions and may augment a bacterium's adaptation to its host or environment. GIs have been identified in strain J2315 of Burkholderia cenocepacia, whereas in strain AU 1054 there has been no published works on such regions according to our text mining and keyword search in Medline. RESULTS: In this study, we identified 21 GIs in AU 1054 by combining two computational tools. Feature analyses suggested that the predictions are highly reliable and hence illustrated the advantage of joint predictions by two independent methods. Based on putative virulence factors, four GIs were further identified as pathogenicity islands (PAIs). Through experiments of gene deletion mutants in live bacteria, two putative PAIs were confirmed, and the virulence factors involved were identified as lipA and copR. The importance of the genes lipA (from PAI 1) and copR (from PAI 2) for bacterial invasion and replication indicates that they are required for the invasive properties of B. cenocepacia and may function as virulence determinants for bacterial pathogenesis and host infection. CONCLUSIONS: This approach of in silico prediction of GIs and subsequent identification of potential virulence factors in the putative island regions with final validation using wet experiments could be used as an effective strategy to rapidly discover novel virulence factors in other bacterial species and strains.


Assuntos
Burkholderia cenocepacia/genética , Ilhas Genômicas/genética , Genômica , Fatores de Virulência/genética , Fatores de Virulência/isolamento & purificação , Células A549 , Aderência Bacteriana , Proteínas de Bactérias/genética , Composição de Bases , Infecções por Burkholderia/microbiologia , Burkholderia cenocepacia/crescimento & desenvolvimento , Burkholderia cenocepacia/patogenicidade , Técnicas de Cultura de Células , Contagem de Colônia Microbiana , Biologia Computacional/métodos , DNA Bacteriano , Deleção de Genes , Transferência Genética Horizontal , Genes Bacterianos/genética , Genoma Bacteriano/genética , Humanos
12.
Bioinformatics ; 33(12): 1758-1764, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28158612

RESUMO

Motivation: Previously constructed classifiers in predicting eukaryotic essential genes integrated a variety of features including experimental ones. If we can obtain satisfactory prediction using only nucleotide (sequence) information, it would be more promising. Three groups recently identified essential genes in human cancer cell lines using wet experiments and it provided wonderful opportunity to accomplish our idea. Here we improved the Z curve method into the λ-interval form to denote nucleotide composition and association information and used it to construct the SVM classifying model. Results: Our model accurately predicted human gene essentiality with an AUC higher than 0.88 both for 5-fold cross-validation and jackknife tests. These results demonstrated that the essentiality of human genes could be reliably reflected by only sequence information. We re-predicted the negative dataset by our Pheg server and 118 genes were additionally predicted as essential. Among them, 20 were found to be homologues in mouse essential genes, indicating that some of the 118 genes were indeed essential, however previous experiments overlooked them. As the first available server, Pheg could predict essentiality for anonymous gene sequences of human. It is also hoped the λ-interval Z curve method could be effectively extended to classification issues of other DNA elements. Availability and Implementation: http://cefg.uestc.edu.cn/Pheg. Contact: fbguo@uestc.edu.cn. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Composição de Bases , Genes Essenciais , Análise de Sequência de DNA/métodos , Software , Animais , Eucariotos/genética , Humanos , Camundongos , Modelos Genéticos
13.
Reprod Biol Endocrinol ; 14: 6, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26837816

RESUMO

BACKGROUND: Several studies on the association of tumor necrosis factor alpha (TNF-α) polymorphisms with recurrent pregnancy loss (RPL) risk have reported conflicting results. The present meta-analysis was conducted to provide a more precise estimation of these relationships and to investigate the real association between TNF-α polymorphisms and RPL. METHODS: An extensive eligible literature search for relevant studies was conducted on PubMed, Embase, and The Cochrane Library from their inceptions to May 12, 2015. Specific inclusion criteria were used to evaluate articles. The odds ratio (OR) with 95% confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed by the STATA12.0 software. RESULTS: 10 case-control studies including 1430 RPL patients and 1727 healthy controls were identified. Meta-analysis indicated that TNF-α-308G/A (rs1800629) polymorphism in the TNF-α gene correlated with elevated RPL risk whereas no significant association was observed between TNF-α-238G/A (rs361625) and RPL. CONCLUSIONS: The current meta-analysis demonstrates that TNF-α-308G/A polymorphism in the TNF-α gene is associated with susceptibility to RPL.


Assuntos
Aborto Habitual/genética , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Razão de Chances , Gravidez , Fatores de Risco
14.
J Med Genet ; 50(7): 479-85, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23667180

RESUMO

BACKGROUND: Graves' disease is a female preponderant autoimmune illness and the contribution of the X chromosome to its risk has long been appreciated. However, no X-linked susceptibility loci have been indentified from recent genome-wide association studies (GWAS). METHODS: We re-examined the X chromosome data from our recent GWAS for Graves' disease by including males that were previously excluded from the X chromosome analyses. The data were analysed using logistic regression analysis including sex as a covariate, and an additive method assuming X chromosome inactivation, implemented in snpMatrix. RESULTS: A cluster of single nucleotide polymorphism (SNPs) at Xq21.1 was found showing association with genome-wide significance, among which rs3827440 was a non-synonymous SNP of GPR174 (P(logistic regression)= 9.52×10(-8); P(snpMatrix)=4.60×10(-9); OR=1.76, 95% CI 1.45 to 2.13). The association was reproduced in an independent sample collection set including 4564 Graves' disease cases and 3968 sex matched controls (combined P(logistic regression)=5.53×10(-21); combined P(snpMatrix)=4.26×10(-22); OR=1.69, 95% CI 1.53 to 1.86). Notably, GPR174 was widely expressed in immune related tissues and rs3827440 genotypes were associated with distinct mRNA levels (p=0.002). GPR174 did not show sex biased gene expression in our expression analysis. Resequencing study suggested the contribution of some rare variants in the GPR174 gene region to disease risk with a collapsing p value of 1.16×10(-3). CONCLUSIONS: The finding of an X-linked risk locus for Graves' disease expands our understanding of the role of the X chromosome in disease susceptibility.


Assuntos
Cromossomos Humanos X/genética , Doença de Graves/genética , Receptores Acoplados a Proteínas G/genética , Alelos , Feminino , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco
15.
J Gastroenterol Hepatol ; 28(4): 717-22, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23216301

RESUMO

BACKGROUND AND AIMS: Gallstone disease (GD) is a common disease of multigenetic origin; however, the major susceptibility loci for GD in human populations remain unidentified. This study aimed to identify the genetic factors contributing to gallstone development in Chinese. METHODS: A genome-wide scan was conducted in 12 Han Chinese GD families to identify linkage loci. The linkage region showing the highest logarithm of odds score encompasses the sterol 12α-hydroxylase gene (CYP8B1). Replication analysis with an independent sample of 192 GD patients and 192 unrelated, matched controls was carried out to verify the associations between CYP8B1 polymorphisms and GD. RESULTS: Three loci (D3S1266, D4S406, and D9S1682) showed suggestive or nominal evidence of linkage in all 12 GD families. The logarithm of odds score of D3S1266 reached 2.71 in the families with late-onset patients. The single nucleotide polymorphism rs3732860 in the 3'-untranslated region of CYP8B1 showed significant association to GD (P = 0.022), and carriers of the A allele had lower risk of GD (odds ratio = 1.46, 95% confidence interval: 1.055-2.034) compared with carriers of the G allele. CONCLUSIONS: The single nucleotide polymorphism rs3732860 in the 3'-untranslated region of the CYP8B1 gene is associated with risk of GD in Chinese Han and appears to be responsible for the observed linkage with D3S1266.


Assuntos
Regiões 3' não Traduzidas/genética , Sistema Enzimático do Citocromo P-450/genética , Cálculos Biliares/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Primers do DNA/química , Feminino , Cálculos Biliares/etnologia , Ligação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Análise de Sequência
16.
Zhonghua Yi Xue Za Zhi ; 91(30): 2092-5, 2011 Aug 16.
Artigo em Chinês | MEDLINE | ID: mdl-22093981

RESUMO

OBJECTIVE: To identify the single nucleotide polymorphisms of human CYP8B1gene and explore the association of some of these SNPs with gallstone disease in Chinese population. METHODS: The exon and part of promoter were sequenced by a fluorescent labeling automatic method to identify and characterize the SNPs in Chinese population. For SNPs with an allelic frequency of over 10%, a case-control study was performed in patients and controls. RESULTS: Eleven SNPs were found within a 5119 bp region. Among them, 1 was in coding region, 5 in promoter and 5 in 3'-UTR. There were 3 novel SNPs and 12 SNPs in SNP database were not found. The allelic frequency of rs3732860 polymorphism showed a significant difference (P = 0.022) in the association study. The subjects with A allele had a significantly lower frequency of gallstone disease than those with G allele (OR = 1.465, 95%CI 1.055 - 2.034, P = 0.023). CONCLUSION: SNP rs3732860 of CYP8B1 gene is associated with gallstone disease in Chinese population. And A allele may play a protective role in the pathogenesis of gallstone.


Assuntos
Cálculos Biliares/genética , Polimorfismo de Nucleotídeo Único , Esteroide 12-alfa-Hidroxilase/genética , Adulto , Idoso , Alelos , Sequência de Bases , Estudos de Casos e Controles , Éxons , Feminino , Cálculos Biliares/etiologia , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade
17.
PLoS Genet ; 4(3): e1000038, 2008 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-18369457

RESUMO

PSORS1 (psoriasis susceptibility gene 1) is a major susceptibility locus for psoriasis. Several fine-mapping studies have highlighted a 300-kb candidate region of PSORS1 where multiple biologically plausible candidate genes were suggested. The most recent study has indicated HLA-Cw6 as the primary PSORS1 risk allele within the candidate region in a Caucasian population. In this study, a family-based association analysis of the PSORS1 locus was performed by analyzing 10 polymorphic microsatellite markers from the PSORS1 region as well as HLA-B, HLA-C and CDSN loci in 163 Chinese families of psoriasis. Five marker loci show strong evidence (P<10(-3)), and one marker locus shows weak evidence (P = 0.04) for association. The haplotype cluster analysis showed that all the risk haplotypes are Cw6 positive and share a 369-kb region of homologous marker alleles which carries all the risk alleles, including HLA-Cw6 and CDSN*TTC, identified in this study. The recombinant haplotype analysis of the HLA-Cw6 and CDSN*TTC alleles in 228 Chinese families showed that the HLA-Cw6(-)/CDSN*TTC(+) recombinant haplotype is clearly not associated with risk for psoriasis (TratioNT = 29:57, p = 0.0025) in a Chinese population, suggesting that the CDSN*TTC allele itself does not confer risk without the presence of the HLA-Cw6 allele. The further exclusion analysis of the non-risk HLA-Cw6(-)/CDSN*TTC(+) recombinant haplotypes with common recombination breakpoints has allowed us to refine the location of PSORS1 to a small candidate region. Finally, we performed a conditional linkage analysis and showed that the HLA-Cw6 is a major risk allele but does not explain the full linkage evidence of the PSORS1 locus in a Chinese population. By performing a series of family-based association analyses of haplotypes as well as an exclusion analysis of recombinant haplotypes, we were able to refine the PSORS1 gene to a small critical region where HLA-C is a strong candidate to be the PSORS1 susceptibility gene.


Assuntos
/genética , Antígenos HLA-C/genética , Proteínas/genética , Psoríase/genética , Psoríase/imunologia , Alelos , Estudos de Casos e Controles , China , Mapeamento Cromossômico , Feminino , Ligação Genética , Predisposição Genética para Doença , Genótipo , Glicoproteínas/genética , Haplótipos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Recombinação Genética
18.
J Invest Dermatol ; 127(11): 2544-51, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17554368

RESUMO

Through a series of linkage analyses in a large Chinese family cohort of psoriasis, we previously identified and confirmed a non-HLA psoriasis linkage locus PSORS9 within a small region at 4q31.2-32.1. Within the critical region of the PSORS9 locus, IL-15 has been long recognized as a strong candidate gene for psoriasis. In this study, we investigated the association between IL-15 genetic polymorphisms and psoriasis in a large Chinese sample. Highly significant evidence for association was identified at a single-nucleotide polymorphism (SNP) (g.96516A --> T) within the 3'-untranslated region (UTR) of the IL-15 gene (P=0.00006, after correction for multiple testing). Haplotype analysis using the SNPs within the 3'UTR region also provided strong supporting evidence for association (P=0.00005), where we identified a haplotype of the 3'UTR region of IL-15 associated with increased risk to psoriasis (odds ratio=1.65). This association was also supported by the results of our expression activity analyses, where we demonstrated that the identified risk haplotype is associated with an increased activity of IL-15. Therefore, we provided early evidence for the important role of IL-15 genetic variants in the pathogenesis of psoriasis, probably by increasing interleukin production and inflammation in the lesions of psoriasis.


Assuntos
/genética , Cromossomos Humanos Par 4/genética , Interleucina-15/genética , Polimorfismo de Nucleotídeo Único/genética , Psoríase/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Interleucina-15/metabolismo , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Psoríase/etnologia , Psoríase/metabolismo
19.
Acta Derm Venereol ; 87(4): 335-40, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17598037

RESUMO

HLA-Cw6 is strongly associated with psoriasis and has been suggested to be the PSORS1 gene that confers susceptibility to early-onset psoriasis. In this study of the clinical features of HLA-Cw*0602-positive and -negative psoriasis patients in a Han Chinese population, we typed HLA-C in a cohort of 679 patients and compared the two groups. Cw*0602-positive patients (n=345) had an earlier disease onset (p < 1 x 10(-5)), more severe disease (p < 1 x 10(-3)), higher frequency of guttate psoriasis (p < 1 x 10(-9)), more affected legs and trunk (p < 1 x 10(-5)), higher incidence of Köbner's phenomenon (p=0.005) and of trauma history (p=0.009). Cw*0602-negative patients (n= 334) had more palmoplantar pustulosis (p=0.004), nail changes (p=0.001) and scalp involvement (p=0.007). However, there was no statistically significant difference between the two groups regarding age, gender, incidence of plaque psoriasis, erythrodermic, inverse, psoriatic arthritis, and the precipitation factors stress and infection. The study showed that Cw*0602-positive patients had some obvious clinical differences from Cw*0602-negative patients in a Han Chinese population, which provides evidence for an HLA-Cw*0602-associated phenotype in psoriasis.


Assuntos
Predisposição Genética para Doença , Antígenos HLA-C/genética , Psoríase/genética , Adolescente , Adulto , Idade de Início , Idoso , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Frequência do Gene , Humanos , Lactente , Infecções/epidemiologia , Dermatoses da Perna/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças da Unha/epidemiologia , Fenótipo , Dermatoses do Couro Cabeludo/epidemiologia , Índice de Gravidade de Doença , Ferimentos e Lesões/epidemiologia
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