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1.
Anticancer Res ; 39(6): 2791-2797, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177115

RESUMO

BACKGROUND/AIM: The aim of this study was to examine the role of caspase-8 rs3834129 polymorphism on colorectal cancer (CRC) risk in Taiwanese CRC patients and healthy controls. MATERIALS AND METHODS: The caspase-8 rs3834129 (-652 6N insertion/deletion) polymorphic genotypes were analyzed in 362 patients with CRC and the same number of age- and gender-matched healthy subjects. The interaction of caspase-8 rs3834129 genotypes with personal behaviors and clinicopathological features were also examined. RESULTS: The percentage of variants ID and DD for caspase-8 rs3834129 genotype were 37.6 and 5.8% in CRC group and 39.0 and 6.6% in the control group, respectively (p for trend=0.7987). The allelic frequency distribution analysis showed that caspase-8 rs3834129 D allele conferred a non-significant lower susceptibility for CRC compared with I allele (OR=0.92, 95%CI=0.74-1.20, p=0.5063). There was no obvious link between caspase-8 rs3834129 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No statistically significant correlation was observed between caspase-8 rs3834129 genotypic distribution and age, gender, tumor size, location or metastasis status. CONCLUSION: Overall, caspase-8 rs3834129 genotypes may not serve as predictors for CRC risk or prognosis.


Assuntos
Caspase 8/genética , Neoplasias Colorretais/genética , Estudos de Associação Genética/métodos , Técnicas de Genotipagem/métodos , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Prognóstico , Taiwan
2.
Anticancer Res ; 39(6): 2903-2909, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177128

RESUMO

BACKGROUND/AIM: The aim of this study was to evaluate the association between selected polymorphisms of the vascular endothelial growth factor gene (rs699947, rs144854329, rs833061, rs2010963, rs3025039) and the risk of prostate cancer development and progression. MATERIALS AND METHODS: The present study included 446 patients with prostate cancer and 241 healthy men. Genotyping was performed by polymerase-chain reaction-restriction fragment length polymorphism analysis. RESULTS: No significant association between the individual polymorphisms studied and the risk of prostate cancer development was detected. A statistically significantly increased risk of prostate cancer development associated with the presence of 9 or 10 risky alleles was found considering the whole group of patients, as well as in patients with low-grade carcinomas (Gleason score <7). CONCLUSION: Individual polymorphisms of VEGF do not appear to contribute to prostate cancer. However, a combination of risky alleles of the studied polymorphisms significantly increases the risk of prostate cancer in Slovak patients.


Assuntos
Estudos de Associação Genética/métodos , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Fator A de Crescimento do Endotélio Vascular/genética , Idoso , Estudos de Casos e Controles , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/patologia , Eslovênia
3.
Hematol Oncol ; 37 Suppl 1: 19-23, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31187528

RESUMO

The revised WHO classification moved all aggressive B-cell lymphomas with a MYC translocation and a concurrent translocation of BCL2 and/or BCL6 into a single diagnostic category. These are the double- and triple-hit lymphomas. These represent a group with typically a poor outcome to conventional therapy, and as a result, intensification of immunochemotherapy has been explored. The optimal approach is far from clear, and recent insight into the biology suggest that they may represent just a subgroup of molecular high-grade B-cell lymphomas that maybe identified by gene expression profiling. There are a number of novel therapeutic approaches under investigation.


Assuntos
Biomarcadores Tumorais , Estudos de Associação Genética , Predisposição Genética para Doença , Linfoma/genética , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Estudos de Associação Genética/métodos , Testes Genéticos , Humanos , Linfoma/diagnóstico , Linfoma/terapia , Gradação de Tumores , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética , Recidiva , Resultado do Tratamento
4.
Medicine (Baltimore) ; 98(24): e15846, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192914

RESUMO

Ischemic heart disease (IHD) has a genetic predisposition and a number of cardiovascular risk factors are known to be affected by genetic factors. Development of metabolic syndrome and insulin resistance, strongly influenced by lifestyle and environmental factors, frequently occur in subjects with a genetic susceptibility. The definition of genetic factors influencing disease susceptibility would allow to identify individuals at higher risk and thus needing to be closely monitored.To this end, we focused on a complex of soluble-N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), playing an important role in metabolic syndrome and insulin resistance, involved in endothelial dysfunction and heart disease. We assessed if genetic variants of the SNARE genes are associated with IHD.SNAP25 rs363050, Stx-1A rs4717806, rs2293489, and VAMP2 26bp ins/del genetic polymorphisms were analyzed in a cohort of 100 participants who underwent heart surgery; 56 of them were affected by IHD, while 44 were not. A statistical association of plasma glycemia and insulin resistance, calculated as Triglyceride glucose (TyG) index, was observed in IHD (P < .001 and P = .03, respectively) after binomial logistic stepwise regression analysis, adjusted by age, gender, diabetes positivity, waist circumference, and cholesterol plasma level. Among genetic polymorphisms, rs4717806(A) and rs2293489(T), as well as the rs4717806 - rs2293489 (A-T) haplotype were associated with higher risk for IHD (Pc = .02; Pc = .02; P = .04, respectively). Finally, a statistical association of rs4717806(AA) genotype with higher TyG index in IHD patients (P = .03) was highlighted by multiple regression analysis considering log-transformed biochemical parameters as dependent variable and presence of coronary artery disease, age, gender, waist circumference, presence of diabetes as predictors. These results point to a role of the Stx-1A rs4717806 SNP in IHD, possibly due to its influence on Stx-1A expression and, as a consequence, on insulin secretion and glucose metabolism.


Assuntos
Estudos de Associação Genética/métodos , Isquemia Miocárdica/genética , Isquemia Miocárdica/cirurgia , Polimorfismo de Nucleotídeo Único , Sintaxina 1/genética , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Cardíacos , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Humanos , Mutação INDEL , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteína 25 Associada a Sinaptossoma/genética , Proteína 2 Associada à Membrana da Vesícula/genética
5.
Nat Genet ; 51(6): 957-972, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31152163

RESUMO

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.


Assuntos
Estudos de Associação Genética/métodos , Predisposição Genética para Doença , Locos de Características Quantitativas , Característica Quantitativa Herdável , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/fisiopatologia , Mapeamento Cromossômico , Grupo com Ancestrais do Continente Europeu , Estudo de Associação Genômica Ampla , Taxa de Filtração Glomerular , Humanos , Padrões de Herança , Testes de Função Renal , Fenótipo , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/urina , Uromodulina/urina
6.
BMC Med Genet ; 20(1): 94, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146742

RESUMO

BACKGROUND: There are several studies with inconsistent conclusions regarding the association between the rs1801133 and rs1801131 polymorphisms within the MTHFR (methylenetetrahydrofolate reductase) gene and colorectal polyp risk. This discrepancy led us to assess the genetic impact of the two polymorphisms on the susceptibility to colorectal polyps. METHODS: A meta-analysis was carried out for quantitative synthesis. According to the inclusion/exclusion criteria, we retrieved, screened and selected all published articles related to colorectal polyps and the MTHFR rs1801133 and rs1801131 polymorphisms. The P value of association test, RRs (risk ratios) and 95% CIs (confidence intervals) were mainly produced. RESULTS: A total of twenty-three case-control studies were included from twenty-two eligible articles. Pooling the results of both rs1801133 and rs1801131 polymorphisms in the overall population suggested a nonsignificant association between colorectal polyp cases and controls, in that all P values in the test of association were larger than 0.05. Nevertheless, pooling results in the "UK" subgroup of rs1801131, comprising five studies (1257 cases/1407 controls), indicated an elevated risk in colorectal polyp cases in comparison with controls, under the genetic models of CC vs. AA (P = 0.032, RR = 1.27, 95% CIs = 1.02, 1.57) and CC vs. AA+AC (P = 0.036, RR = 1.27, 95% CIs = 1.02, 1.60). CONCLUSION: The C/C genotype of MTHFR rs1801131 is more likely to be a genetic risk factor for colorectal polyps in the UK region, although this finding should be verified with a larger sample size.


Assuntos
Pólipos do Colo/genética , Predisposição Genética para Doença/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Frequência do Gene , Estudos de Associação Genética/métodos , Estudos de Associação Genética/estatística & dados numéricos , Genótipo , Humanos , Fatores de Risco
7.
Gene ; 707: 53-57, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31075414

RESUMO

Genetic variants in monoamine neurotransmitter genes have been recurrently associated with panic disorder, addiction and mood disorders. Recent evidence also indicates that norepinephrine neurotransmission can influence a series of psychophysical and psychobiological parameters related to athletic performance, and the presence of variants in the SLC6A2 (solute carrier family 6 member 2) gene, which encodes the norepinephrine transporter, can be detrimental to an adequate noradrenergic signaling. Accordingly, the objective of the present study was to explore the SLC6A2 Thr99Ile variant (rs1805065) in a cohort composed of highly-trained individuals and non-trained individuals. A total of 1556 Brazilians: 926 non-athletes and 630 athletes (322 endurance athletes and 308 power athletes) were compared in this case-control association study. The Thr99Ile variant showed only two genotypes (C/C or C/T), and a low minor allele frequency of ≈1%. However, none of the power athletes had the mutant T-allele (i.e., the C/T genotype), which may be related to decreased norepinephrine transporter activity. The genotype distribution and allele frequency observed in power athletes were significantly different when compared to non-athletes or endurance athletes. Therefore, the presence of the T-allele may decrease the chance of belonging to the group of athletes involved in explosive physical tasks. These results still need to be replicated in independent cohorts. However, it appears reasonable to assume that there is an association between the SLC6A2 gene variant and power athletic status.


Assuntos
Desempenho Atlético , Estudos de Associação Genética/métodos , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Substituição de Aminoácidos , Atletas , Brasil , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Adulto Jovem
8.
Nat Genet ; 51(6): 933-940, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31086352

RESUMO

The genetic architecture of psychiatric disorders is characterized by a large number of small-effect variants1 located primarily in non-coding regions, suggesting that the underlying causal effects may influence disease risk by modulating gene expression2-4. We provide comprehensive analyses using transcriptome data from an unprecedented collection of tissues to gain pathophysiological insights into the role of the brain, neuroendocrine factors (adrenal gland) and gastrointestinal systems (colon) in psychiatric disorders. In each tissue, we perform PrediXcan analysis and identify trait-associated genes for schizophrenia (n associations = 499; n unique genes = 275), bipolar disorder (n associations = 17; n unique genes = 13), attention deficit hyperactivity disorder (n associations = 19; n unique genes = 12) and broad depression (n associations = 41; n unique genes = 31). Importantly, both PrediXcan and summary-data-based Mendelian randomization/heterogeneity in dependent instruments analyses suggest potentially causal genes in non-brain tissues, showing the utility of these tissues for mapping psychiatric disease genetic predisposition. Our analyses further highlight the importance of joint tissue approaches as 76% of the genes were detected only in difficult-to-acquire tissues.


Assuntos
Perfilação da Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Transtornos Mentais/genética , Transtornos Mentais/psicologia , Transcriptoma , Algoritmos , Biologia Computacional/métodos , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Estudos de Associação Genética/métodos , Estudo de Associação Genômica Ampla , Humanos , Transtornos Mentais/diagnóstico , Especificidade de Órgãos , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Característica Quantitativa Herdável
9.
Nat Genet ; 51(6): 947-951, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31133747

RESUMO

How maternal factors in oocytes trigger zygotic genome activation (ZGA) is a long-standing question in developmental biology. Recent studies in 2-cell-like embryonic stem cells (2C-like cells) suggest that transcription factors of the DUX family are key regulators of ZGA in placental mammals1,2. To characterize the role of DUX in ZGA, we generated Dux cluster knockout (KO) mouse lines. Unexpectedly, we found that both Dux zygotic KO (Z-KO) and maternal and zygotic KO (MZ-KO) embryos can survive to adulthood despite showing reduced developmental potential. Furthermore, transcriptome profiling of the MZ-KO embryos revealed that loss of DUX has minimal effects on ZGA and most DUX targets in 2C-like cells are normally activated in MZ-KO embryos. Thus, contrary to the key function of DUX in inducing 2C-like cells, our data indicate that DUX has only a minor role in ZGA and that loss of DUX is compatible with mouse development.


Assuntos
Desenvolvimento Embrionário/genética , Estudos de Associação Genética , Genoma , Proteínas de Homeodomínio/genética , Zigoto/metabolismo , Animais , Sistemas CRISPR-Cas , Regulação da Expressão Gênica no Desenvolvimento , Marcação de Genes , Estudos de Associação Genética/métodos , Camundongos , Camundongos Knockout
10.
Genet Test Mol Biomarkers ; 23(5): 325-331, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30942619

RESUMO

Aims: This study was designed to determine if vitamin D receptor (VDR), carrier globulin/binding protein (GC), and cytochrome P-450 family 2, subfamily R, polypeptide 1 (CYP2R1) gene polymorphisms are risk factors in the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients from Northeast India. Materials and Methods: A total of 351 HCV-infected patients were enrolled of which 167 were diagnosed with chronic hepatitis C (CHC), 124 with liver cirrhosis (LC), and 60 with HCC together with 102 age- and sex-matched healthy controls. VDR (BsmI, ApaI, and TaqI), GC (rs4588, rs7051), and CYP2R1 (rs10741657) gene polymorphisms were genotyped for all subjects. Statistical data were analyzed using SPSS ver. 22.0. Results: The frequency of the ApaI CC genotype, ApaI C allele, and bAt haplotype of the VDR gene was significantly higher in HCC and LC patients than controls. After adjusting for other covariates (age, gender, platelet count, AST, ALT, serum albumin, and viral load) logistic regression analysis showed that the ApaI CC genotype and bAt haplotype were independent predictors of HCC development. No significant associations was found for the GC and CYP2R1 polymorphisms examined with the occurrence of HCC. Conclusions: The presence of the VDR ApaI CC genotype and bAt haplotype appear to be important indicators in the development of HCC among HCV-infected patients. Larger studies are needed to further clarify and establish this potential causal relationship.


Assuntos
Carcinoma Hepatocelular/genética , Receptores de Calcitriol/genética , Adulto , Idoso , Alelos , Carcinoma Hepatocelular/metabolismo , Colestanotriol 26-Mono-Oxigenase/genética , Colestanotriol 26-Mono-Oxigenase/metabolismo , Família 2 do Citocromo P450/genética , Família 2 do Citocromo P450/metabolismo , Feminino , Frequência do Gene/genética , Estudos de Associação Genética/métodos , Predisposição Genética para Doença , Genótipo , Haplótipos , Hepacivirus/patogenicidade , Hepatite C/complicações , Hepatite C/genética , Hepatite C Crônica/genética , Humanos , Índia , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Receptores de Calcitriol/metabolismo , Proteína de Ligação a Vitamina D/genética , Proteína de Ligação a Vitamina D/metabolismo
11.
Gene ; 705: 1-4, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31009679

RESUMO

OBJECTIVES: Placental hypoxia is a hallmark of preeclampsia. SNP rs479200 in the EGLN1 gene is associated with reduced responsiveness to hypoxia. Whether this translates into an association between SNP rs479200 and preeclampsia is not known. We evaluated the association of SNP rs479200 (T>C) with the risk of preeclampsia. METHODS: This case-control study involved 600 pregnant women of whom 300 were preeclamptic and 300 were normotensive. SNP rs479200 was genotyped by PCR-RFLP method. RESULT: Minor allele frequency was 44% in preeclamptic women and 53% in normotensive pregnant women (P = 1.8 × 10-3; odds ratio = 1.43). The odds ratio was heterogeneous when compared after categorization of the preeclamptic group into clinical sub-groups. The association was significant with both mild (P = 6.2 × 10-5) and severe (3.8 × 10-3) preeclampsia. However, the odds ratio was 0.52 for mild preeclampsia and 1.43 for severe preeclampsia. CONCLUSION: The minor allele of SNP rs479200 is associated with the predisposition to preeclampsia. This association underlines the importance of oxygen sensing in the pathogenesis of preeclampsia.


Assuntos
Estudos de Associação Genética/métodos , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Técnicas de Genotipagem , Humanos , Gravidez , Índice de Gravidade de Doença , Adulto Jovem
12.
Int Heart J ; 60(3): 656-664, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31019168

RESUMO

The issue that genetic polymorphism of tumor necrosis factor-α (TNF-α) is associated with dilated cardiomyopathy (DCM) is debatable. We sought to investigate the potential role of TNF-α gene polymorphism (G-308A) in the susceptibility to dilated cardiomyopathy.We retrieved PubMed, EMBASE, and CNKI to collect all articles which reported on the association between TNF-α G-308A polymorphism and dilated cardiomyopathy. Two authors used the Newcastle-Ottawa Scale (NOS) checklist to assess the quality of the included studies. The odds ratio (OR) with 95% confidence intervals (CI) were pooled in a specific genetic model to assess the association and Stata version 14.0 software was used.A total of 9 studies with 1338 patients and 1677 controls were included in this study. The results from this meta-analysis indicated that TNF-α G-308A polymorphism significantly increased the risk of dilated cardiomyopathy in heterozygous comparison (GA versus GG: OR = 1.87; 95%CI = 1.03-3.40; P < 0.05). The increased risk of DCM was also found in Asian populations using a dominant model and heterozygous comparison (GA+AA versus GG: OR = 2.00, 95%CI = 1.02-3.92, P < 0.05; GA versus GG: OR = 1.94, 95%CI = 1.23-3.06, P < 0.05).The current meta-analysis revealed that TNF-α gene polymorphism (G-308A) may be associated with the susceptibility to DCM.


Assuntos
Cardiomiopatia Dilatada/genética , Estudos de Associação Genética/métodos , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Cardiomiopatia Dilatada/etnologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Estudos Observacionais como Assunto
13.
BMC Bioinformatics ; 20(1): 165, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940094

RESUMO

BACKGROUND: Log-linear and multinomial modeling offer a flexible framework for genetic association analyses of offspring (child), parent-of-origin and maternal effects, based on genotype data from a variety of child-parent configurations. Although the calculation of statistical power or sample size is an important first step in the planning of any scientific study, there is currently a lack of software for genetic power calculations in family-based study designs. Here, we address this shortcoming through new implementations of power calculations in the R package Haplin, which is a flexible and robust software for genetic epidemiological analyses. Power calculations in Haplin can be performed analytically using the asymptotic variance-covariance structure of the parameter estimator, or else by a straightforward simulation approach. Haplin performs power calculations for child, parent-of-origin and maternal effects, as well as for gene-environment interactions. The power can be calculated for both single SNPs and haplotypes, either autosomal or X-linked. Moreover, Haplin enables power calculations for different child-parent configurations, including (but not limited to) case-parent triads, case-mother dyads, and case-parent triads in combination with unrelated control-parent triads. RESULTS: We compared the asymptotic power approximations to the power of analysis attained with Haplin. For external validation, the results were further compared to the power of analysis attained by the EMIM software using data simulations from Haplin. Consistency observed between Haplin and EMIM across various genetic scenarios confirms the computational accuracy of the inference methods used in both programs. The results also demonstrate that power calculations in Haplin are applicable to genetic association studies using either log-linear or multinomial modeling approaches. CONCLUSIONS: Haplin provides a robust and reliable framework for power calculations in genetic association analyses for a wide range of genetic effects and etiologic scenarios, based on genotype data from a variety of child-parent configurations.


Assuntos
Estudos de Associação Genética/métodos , Software , Criança , Técnicas de Genotipagem , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único , Tamanho da Amostra
15.
Mol Genet Genomics ; 294(4): 963-983, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30963249

RESUMO

Rice is the staple food for majority of the global population. But, rice grain has low protein content (PC). Mapping of QTLs controlling grain PC is essential for enhancement of the trait through breeding programs. A shortlisted panel population for grain protein content was studied for genetic diversity, population structure and association mapping for grain PC. Phenotyping results showed a wide variation for grain PC. The panel population showed a moderate level of genetic diversity estimated through 98 molecular markers. AMOVA and structure analysis indicated linkage disequilibrium for grain PC and deviation of Hardy-Weinberg's expectation. The analysis showed 15% of the variation among populations and 73% among individuals in the panel population. STRUCTURE analysis categorized the panel population into three subpopulations. The analysis also revealed a common primary ancestor for each subpopulation with few admix individuals. Marker-trait association using 98 molecular markers detected 7 strongly associated QTLs for grain PC by both MLM and GLM analysis. Three novel QTLs qPC3.1, qPC5.1 and qPC9.1 were detected for controlling the grain PC. Four reported QTLs viz., qPC3, QPC8, qPC6.1 and qPC12.1 were validated for use in breeding programs. Reported QTLs, qPC6, qPC6.1 and qPC6.2 may be same QTL controlling PC in rice. A very close marker RM407 near to protein controlling QTL, qProt8 and qPC8, was detected. The study provided clue for simultaneous improvement of PC with high grain yield in rice. The strongly associated markers with grain PC, namely qPC3, qPC3.1, qPC5.1, qPC6.1, qPC8, qPC9.1 and qPC12.1, will be useful for their pyramiding for developing protein rich high yielding rice.


Assuntos
Estudos de Associação Genética/métodos , Oryza/genética , Proteínas de Plantas/genética , Locos de Características Quantitativas , Biofortificação , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Proteínas de Grãos/metabolismo , Desequilíbrio de Ligação , Oryza/metabolismo
16.
Gene ; 703: 65-70, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-30890475

RESUMO

As a progressive and chronic disease, type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia with rising prevalence worldwide. The ε4 allele of the apolipoprotein E (ApoE) gene may be risk factor of severe peripheral neuropathy in T2DM patients. The association of ApoE polymorphism and Alzheimer's disease (AD) in T2DM patients remains largely unknown. Totally 156 T2DM patients with AD and 145 T2DM patients were included. The genotypes and allele frequency of ApoE were analyzed to explore the role of ApoE in AD in T2DM patients. The levels of total cholesterol (TC), triglyeride (TG), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C) were detected to further investigate mechanism of ApoE. Genotype frequency ratio of genotype ε3/4, ε4/4 and allele ε4 among the T2DM patients with AD was obviously increased. The TC, TG and LDL-C levels of T2DM patients with ε3/4 genotype were higher than those with ε3/3 or ε2/3 genotype and the ε3/4 genotype, while the HDL-C level was on the contrary, suggesting that ε3/4 genotype elevated blood lipid levels in T2DM patients with AD, thus increasing the risk of AD in T2DM patients. ApoE polymorphism was associated with AD in T2DM patients. ApoE ε3/4 genotype was possibly to serve as a risk factor for AD in T2DM patients by enhancing the blood lipid levels.


Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Diabetes Mellitus Tipo 2/complicações , Frequência do Gene , Estudos de Associação Genética/métodos , Idoso , Doença de Alzheimer/metabolismo , Estudos de Casos e Controles , Colesterol/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Triglicerídeos/metabolismo
17.
Hum Genet ; 138(4): 363-374, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30838450

RESUMO

Neural tube defect disorders are developmental diseases that originate from an incomplete closure of the neural tube during embryogenesis. Despite high prevalence-1 out of 3000 live births-their etiology is not yet established and both environmental and genetic factors have been proposed, with a heritability rate of about 60%. Studies in mouse models as well as in human have further suggested a multifactorial pattern of inheritance for neural tube defect disorders. Here, we report results obtained from clinical diagnosis and NGS analysis of a cohort composed of 52 patients. Using a candidate gene panel approach, we identified variants in known genes of planar cell polarity (PCP) pathway, although with higher prevalence than previously reported. Our study also reveals variants in novel genes such as FREM2 and DISP1. Altogether, these results confirm the implication of the PCP genes and involve the FRAS/FREM2 complex and Sonic Hedgehog signaling as novel components in the appearance of NTDs.


Assuntos
Polaridade Celular/genética , Estudos de Associação Genética/métodos , Defeitos do Tubo Neural/genética , Análise de Sequência de DNA/métodos , Adulto , Animais , Criança , Estudos de Coortes , Análise Mutacional de DNA/métodos , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Defeitos do Tubo Neural/patologia , Gravidez , Transdução de Sinais/genética , Transcriptoma
18.
Curr Med Sci ; 39(1): 44-51, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30868490

RESUMO

This study sought to explore the relationship between cytochrome P450 2C19 (CYP2C19) *2/*3 polymorphisms and the development of coronary heart disease (CHD), and to evaluate the influence of the single nucleotide polymorphisms (SNPs) on the occurrence of adverse clinical events in CHD patients. A total of 231 consecutive patients candidate for percutaneous coronary intervention genotyped for CYP2C19*2 (681G>A) and *3 (636G>A) polymorphisms were enrolled. The adverse clinical events were recorded during a follow-up period of 14 months. The incidence of CHD, according to coronary angiography, was significantly higher (P=0.025) in CYP2C19*2 carriers group. Stepwise binary logistic regression analysis revealed that among factors that potentially influenced the presence of CHD (age>60 years, gender, BMI, etc.), CYP2C19*2 carriers (OR 1.94, 95% CI: 1.08-3.50, P=0.028) and male gender (OR 2.74, 95% CI: 1.58-4.76, P=0.001) were independent predictors, which were associated with the presence of CHD. The follow-up results showed that the incidence of adverse cardiovascular events within 14 months of discharge was significantly higher in the CYP2C19*2 carriers than in the non-carriers (21.6% vs. 6.3%, P=0.019). The results of the multivariate Cox proportional hazards model showed that CYP2C19*2 loss-of-function was the only independent factor which predicted the coronary events during the follow-up period of 14 months (OR=3.65, 95% CI 1.09-12.25, P=0.036). The adverse impact of CYP2C19*2 polymorphisms was found not only in the risk of the presence of CHD, but also in the adverse cardiovascular events in CHD patients during the follow-up period of 14 months. However the same influence was not found in CYP2C19*3 mutation in Chinese Han population.


Assuntos
Doença das Coronárias/genética , Doença das Coronárias/cirurgia , Citocromo P-450 CYP2C19/genética , Estudos de Associação Genética/métodos , Fatores Etários , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Polimorfismo de Nucleotídeo Único , Fatores Sexuais
19.
Gene ; 698: 186-197, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-30849545

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF) gene plays a key role in angiogenesis and tumor growth. The relationship between VEGF gene polymorphisms and bladder cancer (BCa) risk was studied extensively in recent years. However, the currently available results are controversial. To ascertain whether VEGF polymorphisms are associated with the susceptibility to BCa, we conducted this systematic review and meta-analysis. MATERIALS AND METHODS: Relevant studies were collected systemically from PubMed, Medline, Embase, Web of Science databases and the Cochrane Library. Odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated using random or fixed effects models by Stata statistical software. This systematic review protocol was registered at International prospective register of systematic reviews (PROSPERO) under number CRD42018099279. RESULTS: A total of eight articles including twenty case-control studies with 3206 BCa cases and 3645 controls were enrolled for this meta-analysis. By pooling all eligible studies, we found that rs3025039, rs833052 and rs25648 polymorphisms were significantly associated with BCa risk. However, in subgroup analyses by stage, we identified a decreased association between the rs699947 A-allele and Muscle-invasive Bladder Cancer (MIBC) under allele contrast, homozygous and recessive genetic models (A vs C: OR = 0.76; AA vs CC: OR = 0.49, 95%CI = 0.27-0.90, I2 = 0.0%, P = 0.021; AA vs CA + CC: OR = 0.60, 95%CI = 0.38-0.96, I2 = 0.0%, P = 0.034). As to ethnicity subgroup analysis, rs699947 and rs3025039 polymorphisms were thought as a risk factor for BCa risk in Asian population, while a decreased association was revealed between rs699947 (C > A) A-allele and BCa risk in African population under dominant, recessive, homozygous, heterozygous and allele contrast genetic models. While for other polymorphisms, null results were found. CONCLUSION: Our meta-analysis suggested that rs3025039 (C > T), rs833052 (C > A) and rs25648 (C > T) polymorphisms of VEGF gene increased susceptibility to BCa risk. And our study also demonstrated homozygous TT genotype in rs3025039, homozygous AA genotype in rs833052 and homozygous TT genotype in rs25648 were significantly relevant to elevated BCa risk. In the meanwhile, it is worth noting that rs699947 (C > A) A-allele should be thought as a protective factor for MIBC.


Assuntos
Neoplasias da Bexiga Urinária/genética , Fator A de Crescimento do Endotélio Vascular/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Frequência do Gene/genética , Estudos de Associação Genética/métodos , Predisposição Genética para Doença/genética , Genótipo , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Estudos Prospectivos , Fatores de Risco , Neoplasias da Bexiga Urinária/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
BMC Med Genet ; 20(1): 42, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30894134

RESUMO

BACKGROUND: Congenital cataract is the most common cause of blindness among children worldwide. The aim of this study was to identify causative mutations in a Chinese family with isolated autosomal dominant posterior subcapsular cataract. METHODS: The proband and her parents underwent full ophthalmological examinations. DNA was extracted from the participants' peripheral venous blood. The mutation was identified via panel-based next-generation sequencing (NGS) and was validated via Sanger sequencing. RESULTS: Posterior subcapsular lenticular opacity was observed in both of the proband's eyes. The novel deletion mutation c.797_814del, p.Ser266_Ala271del in the PITX3 gene was identified in the proband and her father. This mutation is located within the otp/aristaless/rax (OAR) domain at the COOH-terminus of the protein, which functions in DNA binding and transactivation. This mutation would result in a deletion of 6 amino acid residues at the C terminal of the protein. CONCLUSIONS: The mutation c.797_814del, p.Ser266_Ala271del is a novel mutation in the conserved DNA-binding OAR domain of PITX3 that causes congenital cataract.


Assuntos
Catarata/congênito , Proteínas de Homeodomínio/genética , Análise de Sequência de DNA/métodos , Deleção de Sequência , Fatores de Transcrição/genética , Catarata/genética , Feminino , Estudos de Associação Genética/métodos , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Homeodomínio/química , Humanos , Masculino , Herança Paterna , Linhagem , Domínios Proteicos , Fatores de Transcrição/química
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