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1.
Clin Rheumatol ; 42(12): 3237-3249, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37495778

RESUMO

OBJECTIVE: Previous studies have demonstrated an association between sex hormone-related traits and systemic lupus erythematosus (SLE). However, because of the difficulties in determining sequential temporality, the causal association remains elusive. In this study, we used two-sample Mendelian randomization (MR) to explore the genetic causal associations between sex hormone-related traits and SLE. METHODS: We used a two-sample MR to explore the causal association between sex hormone-related traits and SLE. The summarized data for sex hormone-related traits (including testosterone, estradiol (E2), sex hormone-binding globulin (SHBG), and bioavailable testosterone (BT)) originated from large genome-wide association studies (GWASs) of European descent. Aggregated data for SLE were derived from the FinnGen consortium (835 cases and 300,162 controls). Random-effects inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, weighted mode, and fixed-effects IVW methods were used for the MR analysis. Random-effects IVW was the primary method used to analyze the genetic causal association between sex hormone-related traits and SLE. Heterogeneity of the MR results was detected using the IVW Cochran's Q estimates. The pleiotropy of MR results was detected using MR-Egger regression and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. Finally, leave-one-out analysis was performed to determine whether MR results were affected by a single single-nucleotide polymorphism (SNP). RESULTS: Random-effects IVW as the primary method showed that testosterone (odds ratio (OR), 0.87; 95% confidence interval (CI), 0.41-1.82; P = 0.705), E2 (OR, 0.95; 95% CI, 0.73-1.23; P = 0.693), SHBG (OR, 1.25; 95% CI, 0.74-2.13; P = 0.400), and BT (OR, 0.99; 95% CI, 0.67-1.47; P = 0.959) had no potential causal association with SLE. The MR-Egger, weighted median, simple mode, weighted mode, and fixed-effects IVW methods all indicated consistent results. The results of the MR-Egger regression showed that there was no pleiotropy in our MR analysis (P > 0.05). The IVW Cochran's Q estimates showed that the MR analysis results of E2, SHBG, and BT on SLE had no heterogeneity (P > 0.05), but testosterone and SLE had heterogeneity (P < 0.05). The leave-one-out analysis confirmed that a single SNP did not affect the MR results. CONCLUSIONS: Our MR analysis demonstrated that genetically predicted testosterone, E2, SHBG, and BT levels were not associated with SLE risk, but the roles of other non-genetic pathways cannot be ruled out. Key Points • This is the first MR study to explore the causal association of sex hormone-related traits with SLE. • No evidence to support causal associations between sex hormone-related traits and SLE. • Our MR analysis may provide novel insights into the causal association between sex hormone-related traits and SLE risk.


Assuntos
Estudo de Associação Genômica Ampla , Lúpus Eritematoso Sistêmico , Humanos , Análise da Randomização Mendeliana , Hormônios Esteroides Gonadais , Testosterona , Lúpus Eritematoso Sistêmico/genética
2.
Ann Hum Genet ; 86(3): 127-136, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35014025

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a complex disease with several risk factors. The effects of blood metabolites on RA remains elusive. We conducted a genetic correlation scan to explore the relevance of blood metabolism with RA. METHOD: The genome-wide association study (GWAS) dataset of RA(2014) was obtained from a large scale meta-analysis, including 29,880 RA cases and 73,758 controls. The GWAS datasets of 529 blood metabolites were derived from a recently published study. Linkage disequilibrium score regression (LDSC) analysis was performed to evaluate the genetic correlation between each of the blood metabolite and RA(2014). Then we used another GWAS data of RA(2021) and blood metabolites for LDSC analysis to verify whether the same blood metabolites were genetically correlated with RA. Mendelian randomization (MR) analysis was then applied to assess the causal relationship between the significant blood metabolites identified by LDSC and RA(2014). RESULT: Six suggestive blood metabolites were identified for RA(2014), including 10-Undecenoate (correlation coefficient = -0.1686, p value = 0.0394), isovalerylcarnitine (correlation coefficient = 0.1660 p value = 0.0273), proline (correlation coefficient = 0.1647, p value = 0.0145), pantothenate (correlation coefficient = -0.3311, p value = 0.0078), tyrosine (correlation coefficient = 0.1735, p value = 0.0010), X-14057 (correlation coefficient = 0.2695, p value = 0.0373). We identified four blood metabolites may have genetic correlations with RA(2021), including oleoylcarnitine (correlation coefficient = 0.1927, p value = 0.0432), levulinate (correlation coefficient = 0.1008, p value = 0.0413), pantothenate (correlation coefficient = -0.2311, p value = 0.0180), tyrosine (correlation coefficient = 0.1301, p value = 0.0078). There are two identical blood metabolites were found to be related with RA: pantothenate and tyrosine. It was found that there was a significant positive causal relationship between RA (exposure) and 10-Undecenoate (outcome) (ß = 0.0077, SE = 0.0033, p = 0.0192) by MR analysis. CONCLUSION: We investigated the genetic correlation and causal relationship between RA and blood metabolites by LDSC and MR analysis. These results may provide novel insights into the genetic mechanism of RA.


Assuntos
Artrite Reumatoide , Estudo de Associação Genômica Ampla , Artrite Reumatoide/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Análise da Randomização Mendeliana/métodos , Polimorfismo de Nucleotídeo Único , Tirosina/genética
3.
Medicine (Baltimore) ; 94(12): e661, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25816037

RESUMO

The aim of this article was to delineate the characteristics of lumbar disc herniation (LDH) in patients with exacerbation of symptoms caused by spinal manipulative therapy (SMT). The main emphasis should be on the prevention of this condition by identifying relevant risk factors. Detailed clinico-radiological profiles of a total number of 10 LDH patients with exacerbation of presentation after SMT were reviewed. All the patients underwent neurological and magnetic resonance imaging examinations. Laminectomy and discectomy were performed, and follow-up was carried out in all patients. The duration of symptoms in the patients before SMT was 4-15 years. After the therapy, an acute exacerbation of back and radicular pain was observed within 24 h. Magnetic resonance imaging showed that L4-L5 was the most frequently affected level observed (7 patients), and each patient had a large disc fragment in the spinal canal. The disc fragments were classified into 3 types according to their localizations. The time internal between the exacerbation of presentation and surgery was 23.1 days. No perioperative complications were noted. All the patients were relieved of radicular pain a few days after surgery. During postoperative follow-up, all patients regained the ability to walk; one patient received catheterization for 1 month and another for 6 months. Eight patients reported a complete resolution of presentation and the rest 2 patients were significantly improved. SMT should be prohibited in some LDH patients to prevent neurological damages, in whom there are 5 possible risk factors. Surgical results for these patients are encouraging.


Assuntos
Deslocamento do Disco Intervertebral/etiologia , Dor Lombar/etiologia , Vértebras Lombares/cirurgia , Manipulação da Coluna/efeitos adversos , Idoso , Discotomia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Deslocamento do Disco Intervertebral/diagnóstico , Deslocamento do Disco Intervertebral/cirurgia , Laminectomia , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Parestesia/etiologia , Incontinência Urinária/etiologia
4.
Sci Rep ; 5: 9116, 2015 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-25766487

RESUMO

The development of a suitable animal model is important for clarifying the pathogenesis of tethered cord syndrome (TCS). This study was undertaken to develop a new animal model for investigating the pathogenesis and therapeutic strategies for TCS. A traction device, a filum terminale tractor, was designed exclusively for this experiment. A TCS model was produced in cats using the tractor to fixate the filum terminale to the dorsal aspect of the second sacrum. The responses to tethering were evaluated by electron microscopy and electromyography for detection of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) at designated time points. Progressive swaying gait and lameness in clinical performance were observed with cord traction. Histopathological examination revealed an association between the increasing traction in the spinal cord and the increase in impaired nerve cells. No changes of SEPs and MEPs were detected in the untethered cats, while the latencies of SEPs and MEPs significantly increased in the tethered cats. The TCS model established in this study is simple and reproducible, in which varying degrees of tension could be applied to the neural elements.


Assuntos
Defeitos do Tubo Neural/fisiopatologia , Animais , Gatos , Modelos Animais de Doenças , Potencial Evocado Motor , Potenciais Somatossensoriais Evocados , Masculino , Defeitos do Tubo Neural/etiologia , Defeitos do Tubo Neural/patologia , Defeitos do Tubo Neural/terapia , Neurônios/patologia , Neurônios/ultraestrutura , Fatores de Tempo
5.
Sci Rep ; 5: 8260, 2015 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-25651970

RESUMO

In the present study, we obtained population genetic data and forensic parameters of 30 InDel loci in Chinese Xibe ethnic group from northwestern China and studied the genetic relationships between the studied Xibe group and other reference groups. The observed heterozygosities ranged from 0.1704 at HLD118 locus to 0.5247 at HLD92 locus while the expected heterozygosities ranged from 0.1559 at HLD118 locus to 0.4997 at HLD101 locus. The cumulative power of exclusion and total probability of discrimination power in the studied group were 0.9867 and 0.9999999999902 for the 30 loci, respectively. Analyses of structure, PCA, interpopulation differentiations and phylogenetic tree revealed that the Xibe group had close genetic relationships with South Korean, Beijing Han and Guangdong Han groups. The results indicated that these 30 loci should only be used as a complement for autosomal STRs in paternity cases but could provide an acceptable level of discrimination in forensic identification cases in the studied Xibe group. Further studies should be conducted for better understanding of the Xibe genetic background.


Assuntos
Povo Asiático/genética , Etnicidade/genética , Genética Populacional , Mutação INDEL , Polimorfismo Genético , Alelos , China , Análise por Conglomerados , Frequência do Gene , Loci Gênicos , Humanos , Filogenia
6.
Electrophoresis ; 35(14): 1993-2000, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24789806

RESUMO

In the present study, 24 Y-chromosomal short tandem repeat (Y-STR) loci were analyzed in 115 unrelated Hui male individuals from Haiyuan county or Tongxin county, Ningxia Hui Autonomous Region, China, to evaluate the forensic application of the 24 STR loci and to analyze interpopulation differentiations by making comparisons between the Hui group data and previously published data of other 13 populations. A total of 115 different haplotypes were observed on these 24 Y-STR loci. The gene diversities ranged from 0.4049 (DYS437) to 0.9729 (DYS385a, b). The overall haplotype diversity was 1 at AGCU 24 Y-STR loci level, while the values were reduced to 0.999237, 0.996949, and 0.996644 at the Y-filer 17 loci, 11 Y-STR loci of extended haplotype and 9 Y-STR loci of minimal haplotype levels, respectively; whereas, haplotype diversity for additional 7 loci (not included in Y-filer 17 loci) was 0.995271. The pairwise FST , multidimensional scaling plot and neighbor-joining tree indicated the Hui group had the closest genetic relationship with Sala in the paternal lineage in the present study. In summary, the results in our study indicated the 24 Y-STRs had a high level of polymorphism in Hui group and hence could be a powerful tool for forensic application and population genetic study.


Assuntos
Povo Asiático/genética , Cromossomos Humanos Y , Etnicidade/genética , Variação Genética , Genética Populacional/métodos , Repetições de Microssatélites , China , Marcadores Genéticos/genética , Haplótipos , Humanos , Masculino , Filogenia
7.
Immunobiology ; 219(9): 671-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24775270

RESUMO

Integration of cellular and humoral arms of the innate immune response is fundamental to the development of powerful effector functions in host defence as well as aberrant immune responses. Here, we provide evidence in support of the relationship between complement activation and NK cell functional modulation. We demonstrate that human NK cells and both CD56(bright)CD16(-) and CD56(dim)CD16(+) populations express receptors known to detect the biologically active peptides C3a and C5a (i.e. C3aR, C5aR, C5L2) and the covalently-bound fragments C3b and metabolites iC3b and C3d which serve in immune adhesion (e.g. CR3, CR4). We also show that several pathogen- or tumour/inflammation-related stimuli differentially regulated those complement receptor expression. Furthermore, our results suggest that C3 fragments (C3a, iC3b) have a negative regulatory effect on IFN-γ production in NK cells. This work provides extensive information of human complement receptors relevant to the integrated actions of complement and NK cells which has been suggested by animal studies. The observations may act as a resource that allows further understanding and exploitation of role of complement in human health and immune mediated diseases.


Assuntos
Ativação do Complemento/imunologia , Células Matadoras Naturais/imunologia , Receptores de Complemento/biossíntese , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Células Matadoras Naturais/metabolismo , Receptores de Complemento/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
Electrophoresis ; 35(14): 2008-13, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24668876

RESUMO

Mongolian is the eighth largest ethnic minority on Chinese population data according to the 2010 census. In the present study, we presented the first report about the allelic frequencies and forensic statistical parameters at the 21 new STRs and analyzed linkage disequilibrium of pairwise loci in the Mongolian ethnic minority, China. Hardy-Weinberg equilibrium tests demonstrated no significant deviations except for the D1S1627 locus. The cumulative power of discrimination and power of exclusion of all the loci are 0.9999999999999999992576 and 0.9999997528, respectively. The results of analysis of molecular variance showed that significant differences between the Mongolian and the other eight populations were found at 1-9 STR loci. In population genetics, the results of principal component analysis, structure analysis, and phylogenetic reconstruction analysis indicated shorter genetic distance between the Mongolian group and the Ningxia Han. All the results suggest that the 21 new STR loci will contribute to Chinese population genetics and forensic caseworks in the Mongolian group.


Assuntos
Povo Asiático/genética , Etnicidade/genética , Polimorfismo Genético , China , Análise por Conglomerados , Frequência do Gene , Humanos , Desequilíbrio de Ligação , Repetições de Microssatélites , Filogenia , Análise de Componente Principal
10.
Balkan Med J ; 30(4): 350-4, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25207140

RESUMO

BACKGROUND: The choroid plexuses, which could secrete a number of neurotrophins, have recently been used in transplantation in central nervous system diseases. AIMS: To study the mechanism of nerve regeneration in the central nervous system by grafting choroid plexus tissues. STUDY DESIGN: Animal experimentation. METHODS: The choroid plexuses from the lateral ventricles of neonatal rats were cultured in adherent culture, and immunocytochemical methods were used to analyse the progenitor cells on days 2, 6, and 10 after seeding. RESULTS: Expression of both nestin and glial fibrillary acidic protein was observed in small cell aggregates on day 2 in primary culture. Most of the nestin-positive cells on day 6 were immunoreactive to glial fibrillary acidic protein antibody. No cells expressing nestin or glial fibrillary acidic protein were seen on day 10. CONCLUSION: These experimental results indicate that the choroid plexus contains a specific cell population - progenitor cells. Under in vitro experimental conditions, the progenitor cells differentiated into choroid plexus epithelial cells but did not form neurons or astrocytes.

11.
Mol Biol Rep ; 39(12): 10265-71, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23065199

RESUMO

The aim of this study was to investigate allelic frequency distribution and forensic genetic parameters of autosomal short tandem repeats (STR) loci of the population samples from 107 Tujia individuals from Chinese Hubei Province. Twenty-one autosomal STR genetic markers (D9S1122, D6S474, D6S1017, D5S2500, D4S2408, D3S4529, D2S441, D2S1776, D22S1045, D20S482, D1S1677, D1S1627, D1GATA113, D19S433, D18S853, D17S1301, D11S4463, D12ATA63, D10S1248, D10S1435 and D14S1434) were simultaneously amplified in a new multiplex polymerase chain reaction system. 155 alleles for all the STR loci from the Tujia population were observed and the corresponding allelic frequencies ranged from 0.005 to 0.589. Expected heterozygosity, polymorphic information content, power of discrimination and power of exclusion of the 21 STR loci in the Tujia population were from 0.579 to 0.824, from 0.525 to 0.802, from 0.773 to 0.945 and from 0.257 to 0.641, respectively. Our results indicate that the autosomal STRs multiplex system provides highly informative STR data and could be useful in forensic individual identification and parentage testing in this region.


Assuntos
Loci Gênicos , Repetições de Microssatélites , China , Genética Forense , Frequência do Gene , Testes Genéticos , Desequilíbrio de Ligação , Paternidade , Análise de Sequência de DNA
12.
Mol Biol Rep ; 39(3): 3017-28, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21701829

RESUMO

Human killer cell immunoglobulin-like receptors are expressed in natural killer cells and subsets of T lymphocytes. They regulate these cells upon interaction with human leukocyte antigen class I molecules and other ligands presented by target cells. KIR gene frequencies and haplotype distributions have been shown to differ significantly between populations from different geographical regions and ethnic origins, which relates to functional variations in the immune response. We have investigated KIR gene frequencies and genotype diversities of 15 KIR genes (KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, ID, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) and two pseudogenes (KIR3DP1 and 2DP1) in 120 unrelated healthy individuals of the Uygur population living in the Xinjiang autonomous region of China. All individuals were typed positive for the four framework loci KIR3DL3, 2DL4, 3DL2 and KIR3DP1, while activating genes (KIR2DS1, 2DS2, 2DS3, 2DS5 and KIR3DS1) indicated some variation in this population. KIR3DS1 was found in a higher frequency in the studied population than in other groups from China. Linkage disequilibrium among KIR genes displayed a wide range. χ(2) analysis, conducted among non-ubiquitous genes, based on the KIR gene frequency data from our study population and previously published population data, revealed significant differences in the KIR2DL1, 2DL2, 2DL3, 2DL5, 3DL1, 2DS1, 2DS2, 2DS3, 2DS5, and 3DS1 genes. A neighbor-joining phylogenic tree, built using the observed carrier frequencies data of 13 KIR loci (KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 3DL1, 3DL2, 3DL3, 2DS1, 2DS2, 2DS3, 2DS5, and 3DS1), showed relationships between the population studied and other previously reported populations. The present study can therefore be valuable for enriching the ethnical gene information resources of the KIR gene pool, for population origin studies and for KIR-related clinical practice.


Assuntos
Etnicidade/genética , Filogenia , Polimorfismo Genético/genética , Receptores KIR/genética , China , Análise por Conglomerados , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase , Receptores KIR/classificação
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