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BACKGROUND: Somatic depression (SD) is different from non-somatic depression (NSD), and insular subregions have been associated with somatic symptoms. However, the pattern of damage in the insular subregions in SD remains unclear. The aim of this study was to use functional connectivity (FC) analyses to explore the bilateral ventral anterior insula (vAI), bilateral dorsal anterior insula (dAI), and bilateral posterior insula (PI) brain circuits in SD patients. METHODS: The study included 28 SD patients, 30 NSD patients, and 30 matched healthy control (HC) subjects. All participants underwent 3.0 T resting state functional magnetic resonance imaging. FC analyses were used to explore synchronization between insular subregions and the whole brain in the context of depression with somatic symptoms. Pearson correlation analyses were performed to assess relationships between FC values in brain regions showing significant differences and the total and factor scores on the 17-item Hamilton Rating Scale for Depression (HAMD17). RESULTS: Compared with the NSD group, the SD group showed significantly decreased FC between the left vAI and the right rectus gyrus, right fusiform gyrus, and right angular gyrus; between the right vAI and the right middle cingulate cortex, right precuneus, and right superior frontal gyrus; between the left dAI and the left fusiform gyrus; and between the right dAI and the left postcentral gyrus. Relative to the NSD group, the SD group exhibited increased FC between the left dAI and the left fusiform gyrus. There were no differences in FC between bilateral PI and any brain regions among the SD, NSD, and HC groups. Within the SD group, FC values between the left vAI and right rectus gyrus were positively correlated with cognitive impairment scores on the HAMD17; FC values between the right vAI and right superior frontal gyrus were positively related to the total scores and cognitive impairment scores on the HAMD17 (p < 0.05, uncorrected). CONCLUSIONS: Aberrant FC between the anterior insula and the frontal and limbic cortices may be one possible mechanism underlying SD.
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Disfunción Cognitiva , Síntomas sin Explicación Médica , Encéfalo , Depresión , Humanos , Imagen por Resonancia Magnética/métodosRESUMEN
OBJECTIVE: To explore the topological properties of the betweenness centrality of the nodes and edges in the brain white matter network of premature ejaculation (PE) patients and analyze the correlation of the importance of the key brain regions and interregional white matter structural connectivity with the ejaculatory function of the patients.Method: We collected the demographic and clinical data, along with the T1 and MR diffusion tensor imaging (MR-DTI) data, on 18 PE patients and 22 normal controls matched in age, sex and education. After preprocessing of the data obtained, we divided the whole brain into 90 symmetrical cortical and subcortical regions (defined as nodes of the brain network) by automated anatomical labeling, examined the structural connectivity between different brain regions by probabilistic white matter fiber tracking (defined as edges of the brain network), and calculated the betweenness centrality of the nodes and edges using the brain connection toolbox. Then, we performed the Mann-Whitney U test on the betweenness centrality of the nodes and edges, subjected the results to false discovery rate (FDR) correction, and assessed the correlation of the attribute values of between-group differences with the ejaculatory function of the patients. RESULTS: Compared with the normal controls, the PE patients showed a significantly decreased betweenness centrality of the right superior occipital gyrus (SOG) (281.18 ± 255.26 vs 67.78 ± 58.98, Z = ï¼3.49, FDR-corrected P < 0.05), but increased betweenness centrality of the right superior temporal gyrus (STG) (222.91 ± 155.60 vs 557.00 ± 322.65, Z = 3.55, FDR-corrected P < 0.05) and betweeness centrality of the edge between the right rolandic operculum and right insula (4.23 ± 8.39 vs 23.83 ± 23.91, Z = 3.84, FDR-corrected P < 0.05). The betweenness centrality of the right SOG was correlated negatively with the level of difficulty in delaying ejaculation (r = ï¼0.51, P = 0.03) and the probability of ejaculation before expectation (r= ï¼0.61, P = 0.01), while that of the right STG positively with PE-related frustration (r = 0.54, P = 0.02) and the level of concern about PE-related distress of the partner (r = 0.47, P = 0.04). CONCLUSIONS: Abnormalities of structural connections were found in the visual stimulus- and emotion processing-related regions in the right cerebral hemisphere of PE patients, which might be associated with rapid ejaculation or decreased ejaculation control and lead to a series of psychological problems.
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Cerebro/fisiología , Eyaculación Prematura/fisiopatología , Sustancia Blanca/fisiología , Estudios de Casos y Controles , Imagen de Difusión Tensora , Eyaculación , Humanos , MasculinoRESUMEN
OBJECTIVE: To explore the topological properties of the degree and strength of nodes in the binary and weighted brain white matter networks of the patients with psychogenic erectile dysfunction (pED) and analyze the changes of myelin integrity, number and length of the white matter fibers in the topological space. METHODS: Diffusion tensor imaging data were obtained from 21 patients with pED and 24 healthy controls matched in sex, age, and years of education and subjected to preprocessing. The whole cerebral cortex was divided into 90 regions, followed by fiber tracking, construction of the binary and weighted white matter networks, and calculation of the node degrees and connectivity strengths in different brain regions. The property values were compared between the two groups using the two-sample t-test, the results were corrected by multiple testing correction, and the correlation of the property values with the erectile function of the patients was subjected to Pearson's correlation analysis. RESULTS: Compared with the healthy controls, the pED patients showed significantly decreased node degree of the left triangular part of inferior frontal gyrus (IFG) (7.54±1.44 vs 5.95±1.28, t = ï¼3.88, corrected P = 0.02), medial orbital part of superior frontal gyrus (SFG) (10.08±3.60 vs 6.29±3.30, t = ï¼3.67, corrected P = 0.02), and amygdala (6.50±2.11 vs 4.29±1.31, t = ï¼4.16, corrected P = 0.01) in the binary networks, as well as the connectivity strength of the left triangular part of IFG (2.50±0.68 vs 1.72±0.50, t = ï¼4.35, corrected P = 0.01), medial orbital part of SFG (3.17±0.97 vs 2.08±1.10, t = ï¼3.53, corrected P = 0.03), and amygdala (1.80±0.69 vs 1.11±0.39, t = ï¼4.03, corrected P = 0.01) in the fractional anisotropy (FA) weighted networks. The node degree of the left amygdala was negatively correlated with the total score (r = ï¼0.47,P = 0.04), second item score (r = ï¼0.46, P = 0.03), and third item score of IIEF-5 (r = ï¼0.45, P = 0.04) in the pED patients. CONCLUSIONS: The myelin integrity of the white matter fibers in the left frontal lobe and amygdale is impaired in pED patients, which leads to the aberrant generation, processing and regulation of their emotions. The decreased pivotal role and importance of the white matter fibers connecting the left amygdale may be associated with pED.
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Amígdala del Cerebelo/diagnóstico por imagen , Disfunción Eréctil/psicología , Sustancia Blanca/diagnóstico por imagen , Anisotropía , Estudios de Casos y Controles , Imagen de Difusión Tensora , Disfunción Eréctil/etiología , Lóbulo Frontal/diagnóstico por imagen , Humanos , Masculino , Vaina de Mielina/patologíaRESUMEN
BACKGROUND: Major depressive disorder (MDD) is characterized by core functional deficits in cognitive inhibition, which is crucial for emotion regulation. To assess the response to ruminative and negative mood states, it was hypothesized that MDD patients have prolonged disparities in the oscillatory dynamics of the frontal cortical regions across the life course of the disease. METHOD: A "go/no-go" response inhibition paradigm was tested in 31 MDD patients and 19 age-matched healthy controls after magnetoencephalography (MEG) scanning. The use of minimum norm estimates (MNE) examined the changes of inhibitory control network which included the right inferior frontal gyrus (rIFG), pre-supplementary motor area (preSMA), and left primary motor cortex (lM1). The power spectrum (PS) within each node and the functional connectivity (FC) between nodes were compared between two groups. Furthermore, Pearson correlation was calculated to estimate the relationship between altered FC and clinical features. RESULT: PS was significantly reduced in left motor and preSMA of MDD patients in both beta (13-30 Hz) and low gamma (30-50 Hz) bands. Compared to the HC group, the MDD group demonstrated higher connectivity between lM1 and preSMA in the beta band (t = 3.214, p = 0.002, FDR corrected) and showed reduced connectivity between preSMA and rIFG in the low gamma band (t = -2.612, p = 0.012, FDR corrected). The FC between lM1 and preSMA in the beta band was positively correlated with illness duration (r = 0.475, p = 0.005, FDR corrected), while the FC between preSMA and rIFG in the low gamma band was negatively correlated with illness duration (r = -0.509, p = 0.002, FDR corrected) and retardation factor scores (r = -0.288, p = 0.022, uncorrected). CONCLUSION: In this study, a clinical neurophysiological signature of cognitive inhibition leading to sustained negative affect as well as functional non-recovery in MDD patients is highlighted. Duration of illness (DI) plays a key role in negative emotional processing, heighten rumination, impulsivity, and disinhibition.
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OBJECTIVE: To study the physiologic base of voice familiarity (VF) and the mechanism of auditory verbal hallucination (AVH) in the patients with schizophrenia (SCH). METHODS: Twenty-six schizophrenic patients, 13 with and 13 without AVH, and 13 healthy control subjects were instructed to passively listen to familiar or unfamiliar voices and to give their judgment and underwent event-related functional magnetic resonance imaging (efMRI) based on blood oxygenation level-dependent (BOLD) signal efficacy. The functional images were collected by using a 1.5-T MRI and were analyzed by using statistical parametric mapping 2 (SPM2). RESULTS: The total score of positive symptoms of the SCH patients with AVH was (45.5 +/- 13.2), significantly higher than that of the SCH patients without AVH [(22.2 +/- 6.7), P < 0.05]. In comparison with unfamiliar voices, familiar voices elicited greater responses in the left superior temporal gyrus, right frontal lobe and limbic lobe among the SCH patients with AVH (P < 0.005, K(E) > 10). IN comparison with healthy control group, when the patients with AVH discriminated the familiar voices their left precuneus lobes were activated more significantly, and when they discriminated unfamiliar voices their right frontal lobes were activated more significantly (P < 0.005, K(E) > 10). In comparison with the SCH patients without AVH when the SCH patients with AVH discriminated the familiar voices their right frontal lobe were activated more significantly (P < 0.005, K(E) > 10), however, when they discriminated unfamiliar voices there was not significantly difference in the activation of the right frontal lobe between these groups. CONCLUSION: The efMRI results of the inter-group comparison support the inner speech disorder hypothesis that the activation of inner speech in the SCH patients with AVH inhibits the activation of external voice on the corresponding cerebral areas. In addition, hallucinating patients may have significant change of VF neurocognitive model.
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Percepción Auditiva/fisiología , Alucinaciones/fisiopatología , Imagen por Resonancia Magnética/métodos , Esquizofrenia/fisiopatología , Adulto , Atención/fisiología , Humanos , Masculino , Pruebas Neuropsicológicas , Psicología del EsquizofrénicoRESUMEN
OBJECTIVE: To detect anti-Scl-70 antibody with enzyme-linked immunosorbent assay (ELISA) using a recombinant fusion peptide which comprises 207 - 765 amino acid fragment of Scl-70 as antigen. METHODS: cDNA encoding Scl-70 antigen fragment from aa207 to aa765 from human placenta cDNA first strand was amplified with PCR. The obtained cDNA was inserted into expression vector Pet-42b and transferred into E.coli BL21 (DE3) for expression of his-tagged fusion peptide. After Ni(2+)-NTA affinity purification, the antigenicity was identified with Western blotting. Serum samples from 36 systemic sclerosis (SSc) patients, 20 patients with other connective tissue disorder (CTD) and 30 normal controls were retrospectively tested with ELISA. RESULTS: A soluble fusion peptide was expressed and purified. The antigenicity was confirmed with Western blotting using standard positive anti-Scl-70 antibody serum. Of the 36 serum samples from SSc patients, 5 of 6 samples showing positive reaction with natural Scl-70 antigen in double immunodiffusion (DID) assay also recognized the recombinant fusion peptide with ELISA, only one serum sample which showed positive anti-Scl-70 in DID displayed a negative result in ELISA assay. On the contrary, 3 patients with negative anti-Scl-70 in DID showed positive results in ELISA assay using this recombinant peptide. All the serum samples from patients with other CTD showed negative results in ELISA assay. CONCLUSION: The recombinant antigen fragment contains major epitope regions in natural Scl-70 antigen. Detection of anti-Scl-70 antibody with ELISA using the recombinant peptide can improve the sensitivity and has a potential role in determining its clinical association.
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Ensayo de Inmunoadsorción Enzimática/métodos , Proteínas Nucleares/análisis , Esclerodermia Sistémica/inmunología , Autoanticuerpos/sangre , ADN-Topoisomerasas de Tipo I , Epítopos , Humanos , Proteínas Recombinantes de Fusión/inmunología , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To study the proteins associated with Sa antigen, a target of the anti-Sa antibodies specific for rheumatoid arthritis, and to elucidate the nature of these proteins. METHODS: Sa antigen was extracted from fresh human placental tissue by anion exchange chromatography and subjected to SDS-PAGE electrophoresis. Serum samples were collected from 155 patients with connective tissue diseases, including rheumatoid arthritis (71 cases), ankylosing spondylitis (11 cases), psoriatic arthritis (7 cases), reactive arthritis (7 cases), juvenile idiopathic arthritis (4 cases), osteoarthritis (5 cases), polymyalgia rheumatica (6 cases), gout (6 cases), systemic lupus erythematous (7 cases), Sjogren's syndrome (10 cases), adult onset Still's disease (3 cases) and Sa antibodies were detected by immunoblotting. The gel bands corresponding to the stained bands were excised, trypsin-digested in gel, and analyzed by LC-ESI-MS/MS. Once identified, the protein was recombinate and expressed in Escherichia coli, and the antibodies were detected by immunoblotting. Then the protein was citrullinated to detect the antibodies again. RESULTS: Immunoblotting showed anti-Sa antibodies, band (s) with apparent molecular weight of 50 000 (and) 55 000, in 34 of the 71 patients of rheumatoid arthritis and 4 of the 84 patients of other rheumatic diseases, with a sensitivity rate of 47.9% and a specificity rate of 95.2%. The target protein was identified as vimentin. The positive rate of anti-vimentin antibody was statistically different between the RA patients and the patients with other rheumatic diseases (P = 0.005), with a sensitivity rate of 36.6% and a specificity rate of 83.3%, respectively. But there was no obvious correlation between anti-vimentin antibody and anti-Sa antibodies (Kappa = 0.316). The positive rate of anti-citrullinated vimentin antibody was significantly higher in the RA patients than in the patients with other rheumatic diseases (P < 0.01), with a sensitivity rate of 49.3%. There was a high correlation between anti-citrullinated vimentin antibody and anti-Sa antibodies (Kappa = 0.746), albeit a low specificity rate (86.9%). CONCLUSION: Citrullinated vimentin is closely correlated with Sa antigen.
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Artritis Reumatoide/sangre , Autoantígenos/aislamiento & purificación , Vimentina/aislamiento & purificación , Especificidad de Anticuerpos/inmunología , Artritis Reumatoide/inmunología , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Humanos , Espectrometría de Masas , Proteoma/aislamiento & purificación , Vimentina/inmunologíaRESUMEN
BACKGROUND: Most previous neuroimaging studies have focused on the structural and functional abnormalities of local brain regions in major depressive disorder (MDD). Moreover, the exactly topological organization of networks underlying MDD remains unclear. This study examined the aberrant global and regional topological patterns of the brain white matter networks in MDD patients. METHODS: The diffusion tensor imaging data were obtained from 27 patients with MDD and 40 healthy controls. The brain fractional anisotropy-weighted structural networks were constructed, and the global network and regional nodal metrics of the networks were explored by the complex network theory. RESULTS: Compared with the healthy controls, the brain structural network of MDD patients showed an intact small-world topology, but significantly abnormal global network topological organization and regional nodal characteristic of the network in MDD were found. Our findings also indicated that the brain structural networks in MDD patients become a less strongly integrated network with a reduced central role of some key brain regions. CONCLUSIONS: All these resulted in a less optimal topological organization of networks underlying MDD patients, including an impaired capability of local information processing, reduced centrality of some brain regions and limited capacity to integrate information across different regions. Thus, these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network.
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Encéfalo/patología , Trastorno Depresivo Mayor/patología , Imagen de Difusión Tensora/métodos , Adulto , Anisotropía , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: To investigate whether the -1438G/A polymorphism in the promoter region of 5-HTR2A gene associates with the weight gain following antipsychotic agents (APS) acute treatment in schizophrenic patients. METHODS: Eighty-four Chinese Han patients with schizophrenia at the first onset were recruited from among 70 nuclear families. The polymorphism of 5-HTR2A gene was determined with PCR-RFLP technique. Body weight was measured in the patients on admission after 10 weeks of treatment with risperidone or chlorpromazine. RESULTS: There were no statistically significant differences in the distribution frequencies of genotype (chi2: 0.172, v1, P > 0.05) and allele (chi2: 0.121, v1, P > 0.05) of -1438G/A polymorphism of 5-HTR2A gene between subgroups (weight gain >or= 7% or < 7%). Likewise, there was no significant difference in weight gain between genotype groups. By means of transmission disequilibrium test and quantitative transmission disequilibrium test, no significant association between the -1438G/A polymorphism of 5-HTR2A gene and weight gain was observed. CONCLUSION: 5-HTR2A gene -1438G/A polymorphism was probably not associated with APS-induced weight gain in Chinese Han patients with schizophrenia in this study.
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Antipsicóticos/uso terapéutico , Polimorfismo Genético , Regiones Promotoras Genéticas/genética , Receptor de Serotonina 5-HT2A/genética , Aumento de Peso/efectos de los fármacos , Adulto , Clorpromazina/uso terapéutico , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Risperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Esquizofrenia/fisiopatología , Aumento de Peso/genéticaRESUMEN
A variety of simple sequence repeats (SSRs) have been identified in the genome of Shigella flexneri serotype 2a (strain Sf301), an enteric pathogen that causes bacillary dysentery in man. The distribution of SSRs, with unit length ranging from 1 to 9 nucleotides, was biased in different regions of the genome. The tri-, tetra- and hexanucleotide SSRs prevailed in the coding regions while the mono- and dinucleotide SSRs were more common in the noncoding regions. Many intergenic SSRs are less than 30 bp away from the downstream open reading frames (ORFs), suggesting a potential role in transcriptional regulation. To study polymorphism of SSRs, we compared 17 coding-region SSRs from strain Sf301 with the corresponding sequences from 23 other strains of four Shigella species. Five chromosomal loci were found to be polymorphic, of which those from S. flexneri strains were most variable. Particularly interesting is the C5-1 locus in the coding sequence of the hcaD gene encoding a subunit of ferredoxin reductase. Depending on the insertion of variable numbers of the unit sequence (CGCAG), the Shigella hcaD genes can encode truncated products due to premature stop codons or frame shifts, or products with extended core alpha helices that leads to radical alterations in the predicted tertiary structure. Hence, SSRs may serve as genotyping markers for epidemiological investigations, and may offer insights into evolutionary adaptation of the pathogens.
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Genoma Bacteriano , Repeticiones de Microsatélite/genética , Shigella/genética , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Secuencia de Bases , ADN Bacteriano/química , ADN Bacteriano/genética , Ferredoxina-NADP Reductasa/química , Ferredoxina-NADP Reductasa/genética , Variación Genética , Modelos Moleculares , Datos de Secuencia Molecular , Mutagénesis Insercional , Polimorfismo Genético , Estructura Secundaria de Proteína , Subunidades de Proteína/química , Subunidades de Proteína/genética , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Serotipificación , Shigella/clasificación , Shigella boydii/genética , Shigella dysenteriae/genética , Shigella flexneri/genética , Shigella sonnei/genética , Especificidad de la EspecieRESUMEN
We have developed a software tool, GenomeComp, for summarizing, parsing and visualizing the genome sequences comparison results derived from voluminous BLAST textual output. With GenomeComp, the variation between genomes can be easily highlighted, such as repeat regions, insertions, deletions and rearrangements of genomic segments. This software provides a new visualizing tool for microbe comparative genomics.
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Genómica/métodos , Programas Informáticos , Biología Computacional/métodos , Bases de Datos Genéticas , Genoma BacterianoRESUMEN
AIM: To identify the susceptible gene (s) for type 2 diabetes in the previously mapped region, 1p36.33-p36.23, in Han population of North China using single nucleotide polymorphisms (SNPs) and to analyze the haplotypes of the gene (s) related to type 2 diabetes. METHODS: Twenty three SNPs located in 10 candidate genes in the mapped region were chosen from public SNP domains with bioinformatic methods, and the single base extension (SBE) method was used to genotype the loci for 192 sporadic type 2 diabetes patients and 172 normal individuals, all with Han ethical origin, to perform this case-control study. The haplotypes with significant difference in the gene (s) were further analyzed. RESULTS: Among the 23 SNPs, 8 were found to be common in Chinese Han population. Allele frequency of one SNP, rs436045 in the protein kinase C/zetagene (PRKCZ) was statistically different between the case and control groups(P<0.05). Furthermore, haplotypes at five SNP sites of PRKCZ gene were identified. CONCLUSION: PRKCZ gene may be associated with type 2 diabetes in Han population in North China. The haplotypes at five SNP sites in this gene may be responsible for this association.
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Pueblo Asiatico/genética , Diabetes Mellitus Tipo 2/genética , Haplotipos , Proteína Quinasa C/genética , Estudios de Casos y Controles , China/etnología , Frecuencia de los Genes , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Phage-displayed random peptide libraries have become an efficient tool for epitope mapping. We used a 6-mer library displayed on PIII of fd phage to screen for the epitope of tumor necrosis factor(TNF-alpha) by monoclonal antibodied. Three rounds of biopanning have been carried out and dot blot and ELISA were used to estimate the enrichment. Seventeen clones from the third rounds of biopanning were randomly selected and the insert DNA sequences were determined. Based on the deduced amino acid sequences, the motifs, LHPGIL and LHPGVC, have found to show homology with TNF-alpha. Finally, the binding inhibition tests proved that binding of antibody (T(5)McAb) was competitively inhibited by phage-borne HLPGIL.
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OBJECTIVE: To investigate the distribution of single nucleotide polymorphisms (SNPs) in CAPN10 gene in Chinese population and their relation with type 2 diabetes mellitus in Han people of Northern China. METHODS: CAPN10 gene was sequenced to detect SNPs in different nationalities of China. Five SNPs were chosen to perform case-control study and haplotype analysis in 156 normal Han people of Northern China and 173 type 2 diabetes. One SNP was also analyzed with transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 68 type 2 diabetes pedigrees (377 people). RESULTS: A total of 40 SNPs were identified in length of 8,936 bp, with an average of 1 in every 223 bp. The SNPs in CAPN10 gene did not distribute evenly and the SNPs in Chinese were different from those reported in Mexican American. There was no significantly statistical difference in the allele frequency of the 5 SNPs between case and control, and the haplotype frequencies in the two groups were not significantly different. No positive results was found in TDT and STDT analysis. CONCLUSIONS: The SNP distribution of CAPN10 gene differs in different nationalities. The studied SNPs in CAPN10 gene may not be the major susceptibility ones of type 2 diabetes mellitus in Han people of Northern China.
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Calpaína/genética , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , China , Etnicidad , Humanos , Reacción en Cadena de la PolimerasaRESUMEN
OBJECTIVE: To investigate whether the -2548G/A functional polymorphism in promoter region of leptin gene influencing weight gain following antipsychotic agents (APS) acute treatment in schizophrenic patients. METHODS: 128 Chinese Han untreated patients with schizophrenia (male 61, female 67) with an age and gender matched health controls (n = 38) were recruited. The polymorphism of leptin gene was determined with PCR-RFLP technique. MRI determined abdominal body fat in 22 controls and 30 patients on admission and after 10 weeks treatment with risperidone or chlorpromazine. Body mass index (BMI) was measured on admission and every week subsequently (for patients). RESULTS: There were average increases in (6.2 +/- 5.7)% of baseline weight and in (38.5 +/- 42)% of baseline abdominal subcutaneous fat (SUB) and in (40.0 +/- 41.2)% of baseline intra-abdominal fat (IAF) 10 weeks after treatment. There were no significant differences in the distribution of allele and genotypes either between the patients and controls or between gender groups. It was found significantly increased weight gain in the patient with the -2548AA genotype (chi(2) = 7.529, df = 1, P = 0.006; OR = 1.941; 95% CI: 1.175 - 3.207); The genotypes had no influence on the baseline weight indicators both in patients and controls. However, as compared with the patients with G allele, the patients with AA genotype had significant increase in BMI (P = 0.003) and SUB (P = 0.009). CONCLUSION: The finding identify that the -2548G/A polymorphism in promoter region of leptin gene associated with APS-induced weight gain and abdominal fat deposition and distribution. -2548AA may be a genetic risk factor for the development of weight gain and body fat deposition in Chinese Han schizophrenic patients during APS acute treatment.
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Antipsicóticos/efectos adversos , Leptina/genética , Polimorfismo Genético , Regiones Promotoras Genéticas , Aumento de Peso/efectos de los fármacos , Tejido Adiposo/metabolismo , Adolescente , Adulto , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To probe the candidate susceptibility gene (s) of type 2 diabetes in the formal mapping region, 1p36.33-p36.23, in Han people of Northern China using single nucleotide polymorphisms (SNPs). METHODS: 23 SNPs located in 10 candidate genes in the mapping region were chosen from public SNP domain by bioinformatic methods and single base extension (SBE) method were used to genotype the loci in 192 sporadic type 2 diabetes patients and 172 normal individuals to perform case-control study. RESULTS: Among the 23 SNPs, 8 were found to be common in Chinese population. There were statistically different in the allele frequency of 2 SNP, rs436045 in the protein kinase C/xi gene and rs228648 in Urotensin II gene between case and control groups. CONCLUSIONS: The two SNP may be associated with type 2 diabetes in Han people of China, which makes base for further study of the relation between the genes they located with type 2 diabetes.
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Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Proteína Quinasa C/genética , Urotensinas/genética , Alelos , Estudios de Casos y Controles , Etnicidad , Pruebas Genéticas , Genotipo , HumanosRESUMEN
OBJECTIVE: To investigate the distribution of the single nucleotide polymorphisms (SNPs) in CAPN10 gene in Chinese population and their relation with type 2 diabetes mellitus in Han people of Northern China. METHODS: CAPN10 gene was sequenced to detect SNPs in 27 samples of different nationalities in China. 5 SNPs were genotyped with single-base extension (SBE) method to perform case-control study in 156 normal Han people of Northern China and 173 type 2 diabetes and the 3 positive loci reported in the article were performed haplotype analysis. One positive locus was also analyzed with transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 68 type 2 diabetes pedigrees (377 cases). RESULTS: A total of 40 SNPs were identified in length of 8,936 bp, with an average of 1 in every 223 bp; The SNPs in CAPN10 gene did not distribute evenly and the SNPs in Chinese was different from that reported in American Mexicans. There was no significantly statistical difference in the allele frequency of the 5 SNPs between case and control (P > 0.05), and the haplotype frequencies in the two groups were not much different (P > 0.05). There was no positive results in TDT and STDT analysis (P > 0.05). CONCLUSIONS: The SNP distribution of CAPN10 gene varies with different nationalities. The studied SNPs in CAPN10 gene may not be the major susceptibility ones of type 2 diabetes mellitus in Han people of Northern China.
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Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Alelos , Pueblo Asiatico , Estudios de Casos y Controles , Etnicidad , Pruebas Genéticas , Genotipo , HumanosRESUMEN
OBJECTIVES: To confirm previous whole-genome scan results of mapping type 2 diabetes susceptibility genes in chromosome 1 in Northern Chinese Han population by conducting a new genome scan with both an enlarged number of type 2 diabetes families and a new set of microsatellite markers. METHODS: A genome scan method was applied. After multiplexed PCR, electrophoreses, genescan and genotyping analysis, size informations for all loci were obtained, and a further study was done using both parametric and non-parametric linkage analysis to calculate the P-values and Z-values of these loci. RESULTS: A total of 34 microsatellite markers distributed within 5 regions along chromosome 1 were surveyed, and 12,000 genotypes were screened. Evidence of linkage with diabetes was identified for 8 of the 34 loci (all the P-values of the 8 loci distributed in 3 regions were lower than 0.05, and the highest Z-value was 2.17). Interestingly, all the 5 markers at the P terminal 1p36.3-1p36.23 region, spanning a long range of 16.9 cM, suggested to be linked with the disease. The results of the other two regions were not consistent with the previous ones. CONCLUSIONS: The study results have confirmed those gained in the previous genome-wide scan. The fact that all 5 loci at the P terminal region displayed linkage with diabetes suggests that more than 1 susceptibility gene may reside in this region.
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Cromosomas Humanos Par 1 , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Repeticiones de Microsatélite/genética , Pueblo Asiatico , Mapeo Cromosómico , Etnicidad , Ligamiento Genético , Pruebas Genéticas , Genotipo , HumanosRESUMEN
OBJECTIVE: To study the function of 5 single nucleotide polymorphisms (SNPs) of the PRKCZ gene, a susceptibility gene for type 2 diabetes in Han population of North China, in the pathogenesis of the disease. METHODS: Bioinformatic methods and reporter gene activity determination were used to analyze the function of the 5 SNPs. RESULTS: The reporter gene activities of different alleles of 2 SNPs, rs427811 and rs809912, were obviously different, which implies that these 2 SNPs might be susceptibility loci of the disease. CONCLUSION: The PRKCZ gene is further confirmed to be a susceptibility gene for type 2 diabetes in Han population of North China. Two SNPs in the gene play a role in the pathogenesis of the disease by affecting the expression level of PRKCZ gene.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleótido Simple , Proteína Quinasa C/genética , Alelos , Pueblo Asiatico , Etnicidad , Predisposición Genética a la Enfermedad , Humanos , Proteína Quinasa C-deltaRESUMEN
OBJECTIVE: To search for the disease-associated haplotype in the PRKCZ gene, a susceptibility gene for type 2 diabetes in Han population of North China, by case-control study and linkage disequilibrium (LD) analysis using single nucleotide polymorphisms (SNPs). METHODS: SNPs located in the PRKCZ gene were chosen from public SNP domain by bioinformatic methods and single base extension (SBE) method was used to genotype the loci in 173 sporadic type 2 diabetes patients and 152 normal individuals to perform case-control study and LD analysis. Haplotype block were constructed in these populations. RESULTS: Several SNPs in the PRKCZ gene were found to be associated with the disease. The SNPs formed different haplotype block pattern in case and control groups. The frequencies of the haplotypes formed by 5 SNPs were statistically different between the two groups. CONCLUSION: The haplotype formed by 5 SNPs in the PRKCZ gene may be associated with type 2 diabetes in Han population of China, which is confirmed from statistics to be a susceptibility gene for the disease.