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1.
Anticancer Res ; 39(10): 5375-5380, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570432

RESUMO

BACKGROUND/AIM: Matrix metalloproteinases-11 (MMP-11) overexpression has been reported in various types of cancer including lung cancer. We aimed to examine the contribution of MMP-11 genotypes to lung cancer risk. MATERIALS AND METHODS: In this case-control study, the MMP-11 rs738791, rs2267029, rs738792 and rs28382575 genotypes were determined among 358 lung cancer patients and 716 age- and gender-matched healthy control Taiwanese. RESULTS: The percentages of rs738791 CT and TT were 50.6% and 9.2% in the case group, slightly higher than 48.5% and 8.1% in the control group (p for trend=0.5638). The allelic analysis showed that the rs738791 T allele did not confer lung cancer risk compared with the C allele. Similarly, there was no association between rs2267029, rs738792 or rs28382575 and lung cancer risk. There was no joint effect of MMP-11 genotypes among ever smokers or non-smokers. CONCLUSION: The genotypes of MMP-11 play a minor role in determining lung cancer risk in Taiwan.


Assuntos
Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Metaloproteinase 11 da Matriz/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taiwan
2.
Medicine (Baltimore) ; 98(31): e16716, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374066

RESUMO

The purposes of the study was to validate the relationship between General transcription factor II-I (GTF2I) genetic variants and kidney involvements of systemic lupus erythematosus (SLE) patients in a Chinese Han population.Samples from 400 SLE patients and 400 age- and sex-matched healthy controls were collected and genotyped by improved multiplex ligation detection reaction technique. The relationship between gene polymorphism of rs117026326, rs73366469, and susceptibility, progression of SLE were analyzed.The present study provided evidence that rs117026326 and rs73366469 were both associated with SLE susceptibility (both C vs T: P < .001). The analysis of dominant, recessive disease model provided us with further validation (P < .001). Both gene polymorphisms are associated with a triad of disease manifestations among SLE patients. Patients carrying genotype TT of rs117026326 had lower 24-hour urinary total protein (24 hours UTP, g/24 hours), 24-hour urinary protein level (g/L·24 hours), lower frequency of the proteinuria and lupus nephritis (LN). Patients carrying genotype TT at rs73366469 had higher 24-hour urinary protein level, higher frequency of the proteinuria, LN and positive anti-dsDNA than those with other genotypes.This study identified the involvement of GTF2I gene polymorphisms in development of SLE, particularly in renal involvement.


Assuntos
Nefrite Lúpica/genética , Fatores de Transcrição TFII/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Nefrite Lúpica/urina , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Proteinúria/urina , Adulto Jovem
3.
Medicine (Baltimore) ; 98(27): e16314, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277174

RESUMO

The Ladybird Homeobox 1 (LBX1) gene has been implicated in the etiology of adolescent idiopathic scoliosis (AIS). The association between LBX1 gene polymorphisms and AIS has been investigated in several studies. However, these findings have yield contradictory results rather than conclusive evidence.This study is to provide a meta-analysis of the published case-control studies on the association between LBX1 gene polymorphisms and AIS in Asian and Caucasian populations.This meta-analysis conformed to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We conducted a literature research on PubMed, Embase, Web of Science, and Cochrane Library until February 10, 2018. We included all case-control or cohort studies about association between LBX1 gene polymorphisms and AIS. The Risk Of Bias In Non-randomised Studies-of Interventions and Critical Appraisal Skills Programme were used to evaluate the risk of bias and study quality. We assessed the strength of association by pooled odds ratios (ORs) and 95% confidence intervals (CIs) in all genetic models under a fixed-effect model or random-effect model. We further performed subgroup analysis by ethnicity and sex. Sensitivity analysis and publication bias were also undertaken.A total of 10 studies (11,411 cases and 26,609 controls) were included in this meta-analysis. The pooled results showed a statistically significant association between LBX1 gene polymorphisms and AIS (for rs11190870, T vs C, OR = 1.54, 95% CI = 1.48-1.61, P < .00001; for rs625039, G vs A, OR = 1.50, 95% CI: 1.38-1.62; P < .00001; for rs678741, G vs A, OR = 0.74, 95% CI: 0.63-0.86; P < .0001; for rs11598564, G vs A, OR = 1.41, 95% CI: 1.31-1.51; P < .0001). For stratified analyses by ethnicity and sex, robust significant associations were detected in Asian and Caucasian populations, and in women and men under all genetic models.T allele of rs11190870 and G alleles of rs625039 and rs11598564 represent risk factors for AIS, but G allele of rs678741 may play a protective role in the occurrence of AIS. Further research is needed to confirm this finding and to understand its implications.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Proteínas de Homeodomínio/genética , Polimorfismo Genético/genética , Escoliose/genética , Fatores de Transcrição/genética , Adolescente , Feminino , Humanos , Masculino , Estudos Observacionais como Assunto , Razão de Chances , Escoliose/etnologia
4.
DNA Cell Biol ; 38(8): 808-813, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31335167

RESUMO

This study aims to investigate whether a relationship exists between the C3435T polymorphism of ABCB1 gene and poststroke depression (PSD). A total of 82 PSD patients and 115 nondepression patient (NPSD) controls were included in this study. All patients were evaluated using the Hamilton Rating Scale for Depression to determine the severity of depression and complete the packet. PSD patients were diagnosed in accordance with the DSM-V criteria. The C3435T polymorphism of ABCB1 was genotyped through fluorescence in situ hybridization and chromosome karyotype analysis system. The PSD (n = 82) and NPSD groups (n = 115) had a total prevalence rate of 41.6%. The prevalence of PSD in men was 58.5%, whereas that in women was 41.5%, and no statistically significant difference existed between the two groups (χ2 = 1.009; p = 0.315). The CC, CT, and TT frequencies of the PSD group were 26.8%, 47.6%, and 25.6%, respectively, whereas those of the NPSD group were 42.6%, 45.2%, and 12.2%, respectively. Based on the CC genotype, the relative risk of homozygous mutant TT was 3.341 (χ2 = 7.869; p = 0.005; OR = 3.341), and the T allele frequency in the PSD group was 49.4% higher than that in the NPSD group. The locus gene frequency was 34.8%, and the relative risk of allele T relative to allele C was 1.830 (χ2 = 8.381; p = 0.004; OR = 1.830). A certain correlation exists between the C3435T gene polymorphism and PSD in the Han population in South Anhui Province, China, and further studies are needed to confirm our findings.


Assuntos
Depressão/genética , Polimorfismo Genético , Acidente Vascular Cerebral/psicologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Grupo com Ancestrais do Continente Asiático/genética , China , Depressão/etiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações
5.
Medicine (Baltimore) ; 98(28): e16318, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305418

RESUMO

RATIONALE: Although Factor V Leiden (FVL) mutation is a major cause of inherited thrombophilia in Western populations; the mutation is extremely rare in Asia. PATIENT CONCERNS: Here we report a case of a 28-year old Korean woman admitted to our hospital with extensive pulmonary embolism. DIAGNOSIS: She was heterozygous for FVL mutation up on evaluation, and screening for asymptomatic family members also revealed heterozygous FVL mutation for her mother. INTERVENTIONS: Enoxaparin 1 mg/kg was initiated, followed by rivaroxaban 15 mg every 12 hours. OUTCOMES: The patient showed improvement in both subjective dyspnea and right ventricular dysfunction and was successfully discharged after five hospital days. LESSONS: FVL mutation screening may be considered in Asian patients with thrombophilia of uncertain etiology in the future.


Assuntos
Fator V/genética , Mutação , Embolia Pulmonar/genética , Trombofilia/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Diagnóstico Diferencial , Feminino , Humanos , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/tratamento farmacológico , República da Coreia , Trombofilia/diagnóstico por imagem , Trombofilia/tratamento farmacológico
6.
Medicine (Baltimore) ; 98(28): e16343, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305422

RESUMO

To estimate the BRAFV600E mutation frequency in Chinese patients with papillary thyroid carcinoma (PTC), and the diagnostic value of BRAFV600E mutation status in thyroid nodules with indeterminate TBSRTC categories.A total of 4875 consecutive samples for thyroid ultrasound-guided fine-needle aspiration cytology (FNAC) and BRAF mutation analysis were collected from patients at Jiangsu Province Hospital on Integration of Chinese and Western Medicine. Among all the cases, 314 underwent thyroidectomy. According to TBSRTC categories, FNAC was performed for a preoperative diagnosis. ROC of the subject was constructed to evaluate the diagnostic value of these 2 methods and their combination.BRAF mutation in FNAC of thyroid nodules occurred in 2796 samples (57.35%). Of 353 nodule samples from 314 patients with thyroid operation, 333 were pathologically diagnosed as PTC. Of these PTC patients, 292 (87.69%) were found to have BRAF mutation in their preoperative FNAC. In 175 cytologically indeterminate thyroid nodules, BRAF mutation identified 88% of PTC. According to ROC data, BRAF mutation testing had an obviously higher sensitivity (87.69%) and specificity (100.00%) than TBSRTC. Combining BRAF mutation testing and TBSRTC achieved the largest AUC (0.954). For 41 PTC with a negative BRAF mutation in preoperative evaluation, the repeated BRAF mutation testing found out 12 samples with BRAF mutation. The true BRAF mutation rate of Chinese PTC patients was 91.29%.Chinese patients with PTC have a higher frequency of BRAF mutation. The BRAF mutation testing affords a high diagnostic value in thyroid nodules with indeterminate cytology.


Assuntos
Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/metabolismo , Nódulo da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biópsia por Agulha Fina , Criança , China , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/metabolismo , Sensibilidade e Especificidade , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Ultrassonografia de Intervenção , Adulto Jovem
7.
Medicine (Baltimore) ; 98(28): e16405, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305452

RESUMO

Our study investigated the association of five genes with MCI in the Xinjiang Uygur population in China. In addition, we also analyzed the association between APOE methylation and MCI.Forty-three MCI and 125 controls were included in the present study. Genotyping was done by Sanger sequencing. DNA methylation assay was done using quantitative methylation-specific polymerase chain reaction (qMSP).The distribution of HMGCR rs3846662 allele frequencies was significantly different between the MCI group and the control group (P = .04), especially in women (P = .032). Subgroup analysis showed that there was a statistically significant association of HMGCR rs3846662 with MCI in the non-APOE ε4 group (P = .024), especially in the females with non-APOE ε4. Similarly, HMGCR rs3846662 genotype and allele frequency in the ApoE E2 protein group were significantly different in the MCI group and the control group (genotype P = .021; allele P = .007). In addition, SIRT1 rs7895833 genotype frequency in the APOE ε4 group was found to be significantly different between the MCI and the control group (P = .005). We also observed a significant association of SIRT1 rs7895833 with MCI in the ApoE E4 protein subgroup (P = .005). In addition, APOE methylation levels were significantly different between the MCI group and the control group (P = .021), especially in men (P = .006). Subgroup analysis showed that APOE methylation levels were significantly associated with MCI in the non-APOE ε4 group (P = .009), especially in men (P = .015).This study found a significant association of HMGCR rs3846662 with MCI in females independent of APOE ε4. In contrast, we revealed that the association of SIRT1 rs7895833 with MCI was dependent on with APOE ε4. We also showed that hypermethylation of APOE in MCI was independent of APOE ε4.


Assuntos
Apolipoproteínas E/genética , Transtornos Cognitivos/genética , Transtornos Cognitivos/metabolismo , Metilação de DNA , Hidroximetilglutaril-CoA Redutases/genética , Sirtuína 1/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino
9.
Gene ; 719: 144009, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31357020

RESUMO

BACKGROUND: The F+1 (rs511898 G>A) polymorphism in a disintegrin and metalloprotease 33 (ADAM33) gene has been implicated in susceptibility of chronic obstruction pulmonary disease (COPD). However, a series of studies have reported inconclusive. The aim of this study is to explore the association between the F+1 (rs511898) of ADAM33 gene and COPD susceptibility by using the method of meta-analysis. METHOD: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure database (CNKI), Chongqing VIP database, Wanfang and China Biology Medicine (CBM) were searched comprehensively to obtain the related cohort studies and case-control studies. The included studies were selected according to inclusion criteria. The pooled odds ratios were performed respectively for allele comparison, additive model, dominant genetic model and recessive genetic model. The association between the F+1 polymorphism of ADAM33 gene and COPD susceptibility was measured by OR and 95%CI by STATA 12.0. The subgroup analysis was distinguished according to the ethnicity. The publication bias was tested by funnel plots and Egger's linear regression method. RESULTS: Twelve case-control studies were included in the meta-analysis, which study is comprised of 6935 participants (2454 patients with COPD and 4481 controls). The meta results showed significant association between ADAM33 F+1 polymorphism and COPD susceptibility in allele model OR total = 1.16(95% CI 1.04-1.30, P = 0.007), OR Asian = 1.14(95% CI 1.02-1.27, P = 0.022), additive model OR total = 1.27 (95% CI 1.13-1.43, P = 0.000), OR Asian = 1.25 (95% CI 1.08-1.45, P = 0.003), recessive model OR total = 1.49 (95% CI 1.16-1.91, P = 0.002), OR Asian = 1.56(95% CI 1.09-2.22, P = 0.014), but not significant in Caucasians. CONCLUSION: The ADAM33 F+1 mutant gene A may increase the risk of COPD among the Asian population, while it may not associate with the European population.


Assuntos
Proteínas ADAM/genética , Medicina Baseada em Evidências , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Proteínas ADAM/química , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Humanos
10.
Gene ; 719: 144007, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31357024

RESUMO

Congenital bilateral absence of vas deferens (CBAVD), a frequent cause of obstructive azoospermia and male infertility in Chinese, is mainly due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study aim to explore the promoter region of CFTR gene in CBAVD patients and study the mutations by functional analysis, and to discuss the significance of mutation testing in this area. We performed screening analysis on 65 CBAVD patients and 50 controls to detect mutations in the CFTR gene, and studied the functions of promoter mutations using reporter gene constructs, transient transfection techniques and subsequent assessment of transcriptional activity and expression levels. Mutations c.-195C>A and c.-34C>T in the promoter region of the CFTR gene were detected in 4 of our Chinese CBAVD patients, one of which was novel (c.-195C>A) and located in the conservative area, as well as the binding site of SP1 transcription factor through the prediction of bioinformatics analysis. By reverse transcription qPCR assay and luciferase assay, we validated it as a functional disease-causing variant that down-regulates the CFTR gene expression, and this effect was related to the amount of transcription factors. This study was the first to explore the promoter region of the CFTR gene in Chinese, and we believe that mutations in this region are associated with Chinese CBAVD patients. We also suggest a systematic strategy for genotyping Chinese CBAVD couples, which should help in developing reproductive counseling.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Doenças Urogenitais Masculinas/genética , Mutação , Regiões Promotoras Genéticas , Ducto Deferente/anormalidades , Adulto , Linhagem Celular , China , Regulação para Baixo , Genes Reguladores , Aconselhamento Genético , Humanos , Masculino , Reprodução , Adulto Jovem
11.
Medicine (Baltimore) ; 98(29): e16266, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335675

RESUMO

It has been proposed that cytotoxic T-lymphocyte antigen 4 (CTLA-4) may attenuate the T-cell activation threshold, thereby decreasing the antitumor response and conferring susceptibility to hepatocellular carcinoma (HCC).In the present study, we selected CTLA-4 tagging single nucleotide polymorphisms (SNPs) and explored the relationship between these polymorphisms and susceptibility to HCC. A hospital-based case-control study, comprising 584 cases with HCC and 923 controls, was performed in an eastern Chinese Han population. CTLA-4 SNPs were genotyped using a custom-by-design 48-Plex SNPscan Kit.We found that the CTLA-4 rs3087243 G>A polymorphism might be associated with increased risk of HCC (GA vs GG: adjusted odds ratio [OR], 1.38; 95% confidence interval [CI], 1.04-1.85; P = .028 and AA/GA vs GG: adjusted OR, 1.43; 95% CI, 1.08-1.89; P = .012). After using Bonferroni correction, this association remained (P = .012 for the AA/GA vs GG genetic model). In addition, the power value was 0.904 in the AA/GA versus GG genetic model. Haplotype analysis showed that CTLA4 Crs16840252Ars231775Ars3087243Trs733618, Crs16840252Grs231775Ars3087243Trs733618, and other haplotypes might increase the risk of HCC risk (P = .018, <.001, and .017, respectively). However, we found that CTLA4 Trs16840252A rs231775Grs3087243Trs733618 decreased the risk of HCC (P = .020).Our results suggest that the CTLA-4 rs3087243 G>A polymorphism increases susceptibility to HCC in an eastern Chinese Han population. CTLA-4 haplotypes may influence the development of HCC. In the future, a population-based fine-mapping study with functional assessment should be performed to further determine these potential correlations.


Assuntos
Antígeno CTLA-4/genética , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
12.
Medicine (Baltimore) ; 98(29): e16457, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335702

RESUMO

The impact of genetic polymorphisms on the occurrence of recurrent ischemic stroke (RIS) is not fully understood. This study was aimed to examine the relationships among the 106PEAR1 and 168PTGS1 polymorphisms and RIS.This was a single-center, retrospective, case-control study of patients seen in consultation between March 2016 and December 2016 at the Shandong Provincial Hospital. The 106PEAR1 (G>A) and 168PTGS1 (-842A>G) polymorphisms were determined by fluorescence in situ hybridization.There were 56 patients with RIS and 137 with initial stroke. Compared with the initial group, the RIS group showed lower LDL-C levels (P = .04). 168PTGS1 (-842A>G) did not meet the Hardy-Weinberg equilibrium. The AA genotype of the 106PEAR1 (G>A) polymorphism was more frequent in the RIS group (17.9% vs 5.8%, P = .009). The A allele also showed a higher frequency than the G allele in the RIS group (P = .02). The multivariable logistic regression analysis showed that 106PEAR1 (G>A) (OR = 3.24, 95%CI: 1.04-10.14, P = .04) and lipid-lowering agents (OR = 9.18, 95%CI: 4.48-18.84, P < .001) were independently associated with RIS.The polymorphism at 106PEAR1 (G>A) was independently associated with RIS in Chinese patients. The assessment of genetic polymorphisms in the prediction of RIS warrants further investigation in order to improve patient management and prognosis after a first ischemic stroke.


Assuntos
Isquemia Encefálica , Ciclo-Oxigenase 1/genética , Receptores de Superfície Celular/genética , Acidente Vascular Cerebral , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Recidiva , Estudos Retrospectivos , Medição de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética
14.
Nat Commun ; 10(1): 2506, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175295

RESUMO

Although there are many known Mendelian genes linked to epileptic or developmental and epileptic encephalopathy (EE/DEE), its genetic architecture is not fully explained. Here, we address this incompleteness by analyzing exomes of 743 EE/DEE cases and 2366 controls. We observe that damaging ultra-rare variants (dURVs) unique to an individual are significantly overrepresented in EE/DEE, both in known EE/DEE genes and the other non-EE/DEE genes. Importantly, enrichment of dURVs in non-EE/DEE genes is significant, even in the subset of cases with diagnostic dURVs (P = 0.000215), suggesting oligogenic contribution of non-EE/DEE gene dURVs. Gene-based analysis identifies exome-wide significant (P = 2.04 × 10-6) enrichment of damaging de novo mutations in NF1, a gene primarily linked to neurofibromatosis, in infantile spasm. Together with accumulating evidence for roles of oligogenic or modifier variants in severe neurodevelopmental disorders, our results highlight genetic complexity in EE/DEE, and indicate that EE/DEE is not an aggregate of simple Mendelian disorders.


Assuntos
Variação Genética , Espasmos Infantis/genética , Proteínas Adaptadoras de Transporte Vesicular/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , DNA (Citosina-5-)-Metiltransferases/genética , Epilepsias Mioclônicas/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Lactente , Japão , Síndrome de Lennox Gastaut/genética , Modelos Logísticos , Mutação , Neurofibromina 1/genética , Polimorfismo de Nucleotídeo Único , Análise de Componente Principal , Canais de Cátion TRPM/genética , Sequenciamento Completo do Exoma
15.
Nat Commun ; 10(1): 2491, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171785

RESUMO

Genetic factors underlying leukocyte telomere length (LTL) may provide insights into telomere homeostasis, with direct links to disease susceptibility. Genetic evaluation of 23,096 Singaporean Chinese samples identifies 10 genome-wide loci (P < 5 × 10-8). Several of these contain candidate genes (TINF2, PARP1, TERF1, ATM and POT1) with potential roles in telomere biology and DNA repair mechanisms. Meta-analyses with additional 37,505 European individuals reveals six more genome-wide loci, including associations at MPHOSPH6, NKX2-3 and TYMS. We demonstrate that longer LTL associates with protection against respiratory disease mortality [HR = 0.854(0.804-0.906), P = 1.88 × 10-7] in the Singaporean Chinese samples. We further show that the LTL reducing SNP rs7253490 associates with respiratory infections (P = 7.44 × 10-4) although this effect may not be strongly mediated through LTL. Our data expands on the genetic basis of LTL and may indicate on a potential role of LTL in immune competence.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Reparo do DNA/genética , Leucócitos/metabolismo , Homeostase do Telômero/genética , Telômero/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Respiratórias/genética , Singapura , Adulto Jovem
16.
BMC Med Genet ; 20(1): 99, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170924

RESUMO

BACKGROUND: Metabolic syndrome (MetS), defined as a cluster of metabolic risk factors including dyslipidemia, insulin-resistance, and elevated blood pressure, has been known as partly heritable. MetS effects the lives of many people worldwide, yet females have been reported to be more vulnerable to this cluster of risks. METHODS: To elucidate genetic variants underlying MetS specifically in females, we performed a genome-wide association study (GWAS) for MetS as well as its component traits in a total of 9932 Korean female subjects (including 2276 MetS cases and 1692 controls). To facilitate the prediction of MetS in females, we calculated a genetic risk score (GRS) combining 14 SNPs detected in our GWA analyses specific for MetS. RESULTS: GWA analyses identified 14 moderate signals (Pmeta < 5X10- 5) specific to females for MetS. In addition, two genome-wide significant female-specific associations (Pmeta < 5X10- 8) were detected for rs455489 in DSCAM for fasting plasma glucose (FPG) and for rs7115583 in SIK3 for high-density lipoprotein cholesterol (HDLC). Logistic regression analyses (adjusted for area and age) between the GRS and MetS in females indicated that the GRS was associated with increased prevalence of MetS in females (P = 5.28 × 10- 14), but not in males (P = 3.27 × 10- 1). Furthermore, in the MetS prediction models using GRS, the area under the curve (AUC) of the receiver operating characteristics (ROC) curve was higher in females (AUC = 0.85) than in males (AUC = 0.57). CONCLUSION: This study highlights new female-specific genetic variants associated with MetS and its component traits and suggests that the GRS of MetS variants is a likely useful predictor of MetS in females.


Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/etnologia , Pessoa de Meia-Idade , Fenótipo , República da Coreia , Fatores de Risco , Fatores Sexuais
17.
BMC Med Genet ; 20(1): 106, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196117

RESUMO

BACKGROUND: Oculocutaneous albinism (OCA) is a human autosomal-recessive hypopigmentation disorder with hypopigmentation in the skin, hair, and eyes. OCA1 and OCA2 are caused by mutations of the TYR and OCA2 genes, respectively, which are responsible for most oculocutaneous albinism. However, the incidence of oculocutaneous albinism patients in Guangxi remains unclear. METHODS: To evaluate the molecular basis of oculocutaneous albinism in thirty-six patients in Guangxi, China. Peripheral venous blood samples were collected from these unrelated patients. The TYR and OCA2 genes of all individuals were analyzed by direct DNA sequencing and the sequences compared with are reference database and bioinformatics analysis. RESULTS: Among the 36 OCA patients, 8(22.2%) were found mutations on TYR gene, 28 (77.8%) on OCA2. And we identified Twenty-seven different TYR and OCA2 mutations in these patients, including one novel TYR framshift mutation c.561_562insTTATTATGTGTCAAATTATCCCCCA, three novel OCA2 mutations: one nonsense mutation c.2195C > G(p.S732X), one deletation mutation(c.1139-1141delTGG), one missense mutations c.2495A > C(p.H832P). The population screening and the bioinformatic analysis to determined the effects of the mutations, which revealed these four novel mutations were pathogenic. CONCLUSIONS: This study expands the mutation spectrum of oculocutaneous albinism. Four novel mutational alleles c.1139-1141delTGG, c.1832 T > C and c.2195C > G and of the OCA2 gene and c.561_562insTTATTATGTGTCAAATTATCCCCCA of TYR were associated with OCA. The genotype-phenotype correlations suggest that molecular diagnosis is more accurate and important in OCA.


Assuntos
Albinismo Oculocutâneo/genética , Análise Mutacional de DNA/métodos , Predisposição Genética para Doença/genética , Mutação , Adolescente , Adulto , Albinismo Oculocutâneo/diagnóstico , Albinismo Oculocutâneo/etnologia , Grupo com Ancestrais do Continente Asiático/genética , Sequência de Bases , Criança , Pré-Escolar , China , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença/etnologia , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas de Membrana Transportadoras/genética , Monofenol Mono-Oxigenase/genética
18.
Sci Data ; 6(1): 91, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201313

RESUMO

Single-molecule long-read sequencing datasets were generated for a son-father-mother trio of Han Chinese descent that is part of the Genome in a Bottle (GIAB) consortium portfolio. The dataset was generated using the Pacific Biosciences Sequel System. The son and each parent were sequenced to an average coverage of 60 and 30, respectively, with N50 subread lengths between 16 and 18 kb. Raw reads and reads aligned to both the GRCh37 and GRCh38 are available at the NCBI GIAB ftp site (ftp://ftp-trace.ncbi.nlm.nih.gov/giab/ftp/data/ChineseTrio/). The GRCh38 aligned read data are archived in NCBI SRA (SRX4739017, SRX4739121, and SRX4739122). This dataset is available for anyone to develop and evaluate long-read bioinformatics methods.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Bases de Dados Genéticas , Genoma Humano , Núcleo Familiar , China , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Análise de Sequência de DNA
19.
BMC Neurol ; 19(1): 114, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164100

RESUMO

BACKGROUND: Epigenetics underlying refractory epilepsy is poorly understood. DNA methylation may affect gene expression in epilepsy patients without affecting DNA sequences. Herein, we investigated the association between Carbamazepine-resistant (CBZ-resistant) epilepsy and EPHX1 methylation in a northern Han Chinese population, and conducted an analysis of clinical risk factors for CBZ-resistant epilepsy. METHODS: Seventy-five northern Han Chinese patients participated in this research. 25 cases were CBZ-resistant epilepsy, 25 cases were CBZ-sensitive epilepsy and the remaining 25 cases were controls. Using a CpG searcher was to make a prediction of CpG islands; bisulfite sequencing PCR (BSP) was applied to test the methylation of EPHX1. We then did statistical analysis between clinical parameters and EPHX1 methylation. RESULTS: There was no difference between CBZ-resistant patients, CBZ-sensitive patients and healthy controls in matched age and gender. However, a significant difference of methylation levels located in NC_000001.11 (225,806,929.....225807108) of the EPHX1 promoter was found in CBZ-resistant patients, which was much higher than CBZ-sensitive and controls. Additionally, there was a significant positive correlation between seizure frequency, disease course and EPHX1 methylation in CBZ-resistant group. CONCLUSION: Methylation levels in EPHX1 promoter associated with CBZ-resistant epilepsy significantly. EPHX1 methylation may be the potential marker for CBZ resistance prior to the CBZ therapy and potential target for treatments.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Resistência a Medicamentos/genética , Epilepsia Resistente a Medicamentos/genética , Epóxido Hidrolases/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Metilação de DNA , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia/tratamento farmacológico , Epilepsia/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Adulto Jovem
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(6): 670-675, 2019 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-31238617

RESUMO

Objective: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect with its genetic evidence widely explored. This study explored the potential the parent-of-origin (PoO) effect of WNT pathway on the risks of NSCL/P, using a case-parent trio design. Methods: Data on the single nucleotide polymorphism (SNP) of WNT genes were selected from a genome-wide association study (GWAS). A total of 806 Chinese non-syndromic cleft lip patients, with or without cleft palate (NSCL/P) case-parent trios, were gathered from an international consortium. PoO effect of WNT pathway genes and its haplotypes were explored by log-linear models. Additional Wald tests were performed to assess: a) the heterogeneity of PoO effect between different maternal exposures, b) the interaction between PoO effect, c) maternal exposure to environmental tobacco smoke (ETS), and d) multivitamin supplementation during pregnancy. The threshold for statistical significance was adjusted as 3.47×10(-4), according to Bonferroni correction. Results: After quality control, a total of 144 SNPs within seven genes were included for analyses, among which 8 SNPs were of potential PoO effect (P<0.05). However, none of them achieved the statistical significance after Bonferroni correction. The haplotype rs4074668-rs12725747 (T-A) on WNT9A showed significant PoO effect, based on the haplotype test for PoO (P=2.74×10(-4)). In addition, no statistically significant interaction was found in further exploration of this haplotype under environmental exposures as ETS or multivitamin supplementation. Conclusions: Genes in the WNT pathway may influence the NSCL/P risks through the potential PoO effect. Particularly, the haplotype rs4074668-rs12725747 (T-A) on WNT9A presented significant PoO effect on NSCL/P, statistically. From this current study, findings on WNT pathway related risks among the NSCL/P, need to be further validated by independent samples in the future.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Fenda Labial/genética , Fissura Palatina/genética , Predisposição Genética para Doença , Via de Sinalização Wnt/genética , Fenda Labial/fisiopatologia , Fissura Palatina/fisiopatologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único , Gravidez
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