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1.
Gene ; 716: 144037, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31398377

RESUMO

COQ2 encodes para-hydroxybenzoate-polyprenyl transferase and, recently, mutations in this gene have been associated with the increase of the risk of multiple system atrophy (MSA) in Japanese cases. Subsequently, studies in Asian patients confirmed the role of COQ2 in the development of MSA, while other analysis failed to replicate these results in Caucasian population. We performed genetics screening of COQ2 in 100 MSA Italian patients. We did not find any pathogenic mutations; our results suggest that COQ2 is not a genetic risk factor for MSA in Italian population.


Assuntos
Alquil e Aril Transferases/genética , Atrofia de Múltiplos Sistemas/genética , Mutação , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade
2.
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
3.
Hum Genet ; 138(10): 1155-1169, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342140

RESUMO

Vitamin D inadequacy, assessed by 25-hydroxyvitamin D [25(OH)D], affects around 50% of adults in the United States and is associated with numerous adverse health outcomes. Blood 25(OH)D concentrations are influenced by genetic factors that may determine how much vitamin D intake is required to reach optimal 25(OH)D. Despite large genome-wide association studies (GWASs), only a small portion of the genetic factors contributing to differences in 25(OH)D has been discovered. Therefore, knowledge of a fuller set of genetic factors could be useful for risk prediction of 25(OH)D inadequacy, personalized vitamin D supplementation, and prevention of downstream morbidity and mortality. Using PRSice and weights from published African- and European-ancestry GWAS summary statistics, ancestry-specific polygenic scores (PGSs) were created to capture a more complete set of genetic factors in those of European (n = 9569) or African ancestry (n = 2761) from three cohort studies. The PGS for African ancestry was derived using all input SNPs (a p value cutoff of 1.0) and had an R2 of 0.3%; for European ancestry, the optimal PGS used a p value cutoff of 3.5 × 10-4 in the target/tuning dataset and had an R2 of 1.0% in the validation cohort. Those with highest genetic risk had 25(OH)D that was 2.8-3.0 ng/mL lower than those with lowest genetic risk (p = 0.0463-3.2 × 10-13), requiring an additional 467-500 IU of vitamin D intake to maintain equivalent 25(OH)D. PGSs are a powerful predictive tool that could be leveraged for personalized vitamin D supplementation to prevent the negative downstream effects of 25(OH)D inadequacy.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Europeu/genética , Genética Populacional , Padrões de Herança , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Vitamina D/análogos & derivados , Estudos de Coortes , Bases de Dados Genéticas , Suplementos Nutricionais , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Raios Ultravioleta , Vitamina D/sangue
4.
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
5.
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
6.
Gene ; 710: 202-209, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31163192

RESUMO

Estrogen regulates bone homeostasis and has a cardio-protective effect. Its physiological functions are mediated through receptors (ER) whose expression can be regulated by presence or absence of polymorphisms. However, the association between ER polymorphisms and BMD as well as lipids are inconsistent. The aim of the study was to investigate whether polymorphisms in ESR are associated with bone mineral density (BMD) and lipids in a cohort of Indian women. We studied PvuII, XbaI polymorphisms in ESR1 and AluI, RsaI polymorphisms in ESR2 genes and their association with bone mineral density (BMD) and lipids in premenopausal (n = 293, mean age: 33.01 ±â€¯5.23 years) and postmenopausal (n = 145, mean age: 56.91 ±â€¯7.1 years) women from Northeast India. AluI and RsaI polymorphisms in ESR2 gene were associated with BMD in postmenopausal women. Logistic regression analysis adjusted for age, BMI, tobacco and alcohol consumption revealed that xx genotype in XbaI polymorphism is associated with osteopenia at spine (OR = 3.3, 95% CI = 1.067-10.204) in postmenopausal women suggesting that allele X is protective (OR = 0.419, 95% CI = 0.177-0.991). Genotype aa in AluI polymorphism, seemed to be protective (OR = 0.092 for osteopenia; OR = 0.152 for osteoporosis) at spine whereas A allele was associated with osteopenia at femur (OR = 2.123, 95% CI = 1.079-4.166) in postmenopausal women. Allele r of RsaI polymorphism, was associated with osteoporosis at spine (OR = 3.222, 95% CI = 1.302-7.96). Thus, AIuI polymorphism of ESR2 gene was associated with spinal and femoral BMD whereas RsaI only with spinal BMD in postmenopausal women and ESR genotypes were not associated with lipids.


Assuntos
Doenças Ósseas Metabólicas/genética , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Lipídeos/análise , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/genética , Pré-Menopausa/genética , Absorciometria de Fóton , Adulto , Densidade Óssea , Doenças Ósseas Metabólicas/metabolismo , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Fêmur/diagnóstico por imagem , Estudos de Associação Genética , Humanos , Índia , Modelos Logísticos , Pessoa de Meia-Idade , Coluna Vertebral/diagnóstico por imagem
7.
Medicine (Baltimore) ; 98(25): e15949, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232926

RESUMO

The chemokine receptor CXCR3 and its ligands CXCL10 and CXCL11 have been suggested to give rise to the most relevant chemokine axis able to facilitate the entrance of immune cells into inflamed tissues and be activated in different inflammatory disorders, such as celiac disease (CD).The aim of this study was to investigate the expression level of CXCR3, CXCL10, and CXCL11 genes in celiac patients compared to healthy controls. Both cohorts have been recruited from the Iranian population.In this case-control study, biopsy specimens were collected from 71 celiac patients (60.5% female) and 90 control subjects (57% female) during 2016. Total RNA was extracted and mRNA expression levels of CXCR3, CXCL10, and CXCL11 genes were investigated by SYBR green qPCR.Based on qPCR and relative quantification method, the mRNA expression levels of CXCR3, CXCL10, and CXCL11 were significantly higher in duodenal biopsies of celiac patients compared to healthy controls in the study population (P = .038, P = .021, and P = .012 respectively).The result of this study showed that CXCR3/CXCL10/CXCL11 signaling axis is overexpressed in the small intestinal mucosa of CD patients compared to controls. This finding might explain the specific enrollment of the main cell populations that infiltrate the epithelium.


Assuntos
Doença Celíaca/genética , Quimiocina CXCL10/genética , Quimiocina CXCL11/genética , Receptores CXCR3/genética , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Regulação da Expressão Gênica , Humanos , Irã (Geográfico) , Masculino
8.
Gene ; 707: 30-35, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31055022

RESUMO

BACKGROUND: Alcohol intake and tobacco smoking have significant negative health consequences and both are influenced by genetic predispositions. Some studies suggest that the FTO gene is associated with alcohol consumption. We investigated whether a tagging variant (rs17817449) within the FTO gene is associated with alcohol intake, problem drinking and smoking behaviour. METHODS: We analysed data from 26,792 Caucasian adults (47.2% of males; mean age 58.9 (±7.3) years), examined through the prospective cohort HAPIEE study. The primary outcomes were daily alcohol consumption, binge drinking, problem drinking (CAGE score 2+) and smoking status in relation to tagging variants within the FTO and ADH1B genes. RESULTS: We found no significant association of the FTO polymorphism with smoking status in either sex. The associations of the FTO polymorphism with drinking pattern were inconsistent and differed by gender. In men, GG homozygote carriers had lower odds of problem drinking (OR 0.85, 95% CI 0.75-0.96, p = 0.03). In women, the combination of the FTO/ADH1B GG/+A genotypes doubled the risk of binge drinking (OR 2.10, 95% CI 1.19-3.71, p < 0.05), and the risk was further increased among smoking women (OR 4.10, 95% CI 1.64-10.24, p = 0.008). CONCLUSIONS: In this large population study, the FTO gene appeared associated with binge and problem drinking, and the associations were modified by sex, smoking status and the ADH1B polymorphism.


Assuntos
Álcool Desidrogenase/genética , Consumo de Bebidas Alcoólicas/genética , Alcoolismo/genética , Bebedeira/genética , Polimorfismo de Nucleotídeo Único , Idoso , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Interação Gene-Ambiente , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais , Fumar/genética
9.
Gene ; 708: 30-37, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31078654

RESUMO

AIM The current study investigated the association of RAGE G82S polymorphism with chronic periodontitis in South Indians with and without type II Diabetes mellitus. MATERIALS AND METHODS: 405 individuals were enrolled into 3 groups-systemically and periodontally healthy with no attachment loss (n = 135), generalized chronic periodontitis (n = 135)and generalized chronic periodontitis with type II diabetes mellitus(n = 135). Periodontal clinical parameters were recorded. RFLP-PCR was utilized for genotyping. RESULTS: Frequencies of genotype GG, GA and AA were 133, 2, 0 in group I respectively, 131, 4, 0 in group II respectively and 118, 13, 4 in group III respectively. Pearson's Chi squared test demonstrated a significant difference in the genotype distribution between the three groups (χ2 = 19.88,P < 0.001). Fischer exact-test showed that the variant GA/AA genotype was associated with a significantly increased risk for generalized chronic periodontitis in type II diabetics when compared with the GG genotype of systemically and periodontally healthy subjects (OR-9.58, 95% CI 2.168-42.339, P < 0.001) and non-diabetic chronic periodontitis subjects (OR- 4.71, 95% CI: 1.54-14.42, P < 0.05). No association and increased susceptibility to chronic periodontitis was observed in subjects with GA/AA genotype when compared with systemically and periodontally healthy subjects (OR- 2.031, 95% CI: 0.366-11.277 P > 0.05). Furthermore, comparison of clinical parameters based on genotype distribution revealed statistically significant higher mean plaque (P < 0.05) and sulcus bleeding score (P < 0.001) in group-III subjects. CONCLUSION: RAGE G82S gene polymorphism confers susceptibility to generalized chronic periodontitis in type II diabetic subjects of South Indian Tamilian ethnicity.


Assuntos
Periodontite Crônica/genética , Diabetes Mellitus Tipo 2/complicações , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Receptor para Produtos Finais de Glicação Avançada/genética , Adulto , Estudos de Casos e Controles , Periodontite Crônica/complicações , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade
10.
Drug Discov Ther ; 13(2): 80-88, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080207

RESUMO

Numerous published studies have investigated the relationship between the paraoxonase 1 (PON1) gene Q192R (rs662) polymorphism and the risk of coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients. However, the results are still conflicting and inconclusive. Potentially eligible articles were searched for in related databases. Odds ratios (OR) with 95% confidence intervals (CI) were used to estimate the associations. Subgroup analysis was performed based on ethnicity. Ten case-control studies were included. A significant increase in the susceptibility for CAD in T2DM patients was found in the allelic model (OR = 1.49, p < 0.001), homozygote model (OR = 2.47, p < 0.001), heterozygote model (OR = 1.47, p < 0.001), dominant model (OR = 1.64, p < 0.001), and recessive model (OR = 1.74, p = 0.001). In subgroup analysis by ethnicity, a significant increase susceptibility was found in Asian populations in the allelic model (OR = 1.39, p = 0.001), homozygote model (OR = 2.15, p = 0.002), heterozygote model (OR = 1.37, p = 0.006), recessive model (OR = 1.65, p = 0.012), and dominant model (OR = 1.54, p < 0.001). A similar significant increase in susceptibility was found in Caucasian populations in the allelic model (OR = 1.75, p = 0.002), homozygote model (OR = 3.39, p = 0.002), recessive model (OR = 1.98, p = 0.030), heterozygote model (OR = 1.64, p = 0.001), and dominant model (OR = 1.83, p < 0.001). The results suggest that the PON1 Q192R polymorphism is associated with a significantly increased risk of CAD in T2DM patients in both Asian and Caucasian populations.


Assuntos
Arildialquilfosfatase/genética , Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/complicações , Polimorfismo de Nucleotídeo Único , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Grupo com Ancestrais do Continente Europeu/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Razão de Chances
11.
BMC Genomics ; 20(1): 395, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113383

RESUMO

BACKGROUND: Many genome-wide association studies have detected genomic regions associated with traits, yet understanding the functional causes of association often remains elusive. Utilizing systems approaches and focusing on intermediate molecular phenotypes might facilitate biologic understanding. RESULTS: The availability of exome sequencing of two populations of African-Americans and European-Americans from the Atherosclerosis Risk in Communities study allowed us to investigate the effects of annotated loss-of-function (LoF) mutations on 122 serum metabolites. To assess the findings, we built metabolomic causal networks for each population separately and utilized structural equation modeling. We then validated our findings with a set of independent samples. By use of methods based on concepts of Mendelian randomization of genetic variants, we showed that some of the affected metabolites are risk predictors in the causal pathway of disease. For example, LoF mutations in the gene KIAA1755 were identified to elevate the levels of eicosapentaenoate (p-value = 5E-14), an essential fatty acid clinically identified to increase essential hypertension. We showed that this gene is in the pathway to triglycerides, where both triglycerides and essential hypertension are risk factors of metabolomic disorder and heart attack. We also identified that the gene CLDN17, harboring loss-of-function mutations, had pleiotropic actions on metabolites from amino acid and lipid pathways. CONCLUSION: Using systems biology approaches for the analysis of metabolomics and genetic data, we integrated several biological processes, which lead to findings that may functionally connect genetic variants with complex diseases.


Assuntos
Pleiotropia Genética , Genoma Humano , Metaboloma/genética , Metabolômica , Mutação , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Afro-Americanos/genética , Algoritmos , Grupo com Ancestrais do Continente Europeu/genética , Humanos
12.
Nat Commun ; 10(1): 2154, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31089142

RESUMO

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.


Assuntos
Neoplasias Colorretais/genética , Loci Gênicos , Predisposição Genética para Doença , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Conjuntos de Dados como Assunto , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Padrões de Herança , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
13.
Nat Commun ; 10(1): 1671, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975994

RESUMO

Host and environmental factors contribute to variation in human immune responses, yet the genetic and evolutionary drivers of alternative splicing in response to infection remain largely uncharacterised. Leveraging 970 RNA-sequencing profiles of resting and stimulated monocytes from 200 individuals of African- and European-descent, we show that immune activation elicits a marked remodelling of the isoform repertoire, while increasing the levels of erroneous splicing. We identify 1,464 loci associated with variation in isoform usage (sQTLs), 9% of them being stimulation-specific, which are enriched in disease-related loci. Furthermore, we detect a longstanding increased plasticity of immune gene splicing, and show that positive selection and Neanderthal introgression have both contributed to diversify the splicing landscape of human populations. Together, these findings suggest that differential isoform usage has been an important substrate of innovation in the long-term evolution of immune responses and a more recent vehicle of population local adaptation.


Assuntos
Processamento Alternativo/imunologia , Imunidade/genética , Infecção/imunologia , Seleção Genética/imunologia , Transcriptoma/imunologia , Grupo com Ancestrais do Continente Africano/genética , Animais , Evolução Biológica , Grupo com Ancestrais do Continente Europeu/genética , Variação Genética/imunologia , Voluntários Saudáveis , Humanos , Masculino , Homem de Neandertal/genética , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Locos de Características Quantitativas/imunologia , Análise de Sequência de RNA , Sequenciamento Completo do Exoma
14.
Genet Test Mol Biomarkers ; 23(5): 332-341, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30932690

RESUMO

Aims: The aim of this study was to summarize the currently available evidence on the associations between the IL-10-1082G/A, IL-10-592A/C, and IL-10-819G/A polymorphisms and susceptibility to atopic dermatitis (AD). Materials and Methods: Five electronic databases including PubMed, the Web of Science, Excerpta Medica dataBASE, the Cochrane Library, and the China National Knowledge Infrastructure were searched for potential studies. Studies illustrating the association of the IL-10-1082G/A, IL-10-592A/C, and IL-10-819G/A polymorphisms and AD susceptibility were included in this meta-analysis. For a study to be included, it had to have been published before September 20, 2018. Study quality was assessed using the Newcastle-Ottawa scale. Summary odds ratios and 95% confidence intervals were calculated to evaluate potential associations under five genetic models. Results: A total of 15 case-control studies comprising of 1647 AD patients and 2031 controls were included in this meta-analysis. Their methodological qualities were generally high. We confirmed an association between the IL-10-819G/A polymorphism and AD, but there was an insignificant association identified between the IL-10-1082G/A and the IL-10-592A/C polymorphisms and AD when all ethnic groups were considered together. The subgroup analyses revealed some ethnic-specific effects. For the IL-10-819G/A polymorphism, individuals with the GG-genotype seemed to have an increased risk of AD among Caucasian populations, but less so in the Asian populations. However, for the IL-10-1082G/A polymorphism, the GG-genotype carriers seemed to be more susceptible to AD in the Asian populations than in the Caucasian populations. Conclusions: This meta-analysis suggests that the IL-10-819G/A polymorphism seems to be associated with increased risk of AD among Caucasian populations, and that the IL-10-1082G/A polymorphism seems to be correlated with AD among Asian populations.


Assuntos
Dermatite Atópica/genética , Interleucina-10/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Fatores de Risco
15.
Forensic Sci Int Genet ; 41: 34-41, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30952105

RESUMO

We investigate the ability of the 31 SNP loci in the Global AIMs Nano set to distinguish self-declared Australian Aboriginal individuals from European, Oceanic, African, Native American and East Asian populations. Human evolution suggests that Australian Aboriginal individuals came to Australia approximately 50 000 years ago, during the time it made up part of Sahul. Since then the colonisation of Australia by Europeans has meant significant admixture within the Australian Aboriginal population. These two events present themselves in our study with the Aboriginal population creating a continuous genetic cline between the Oceanic and European groups. We also assigned the Aboriginal individuals into their traditional regional groups to determine whether there was any ability to distinguish these from each other. We found similar results to studies using other markers, namely that the more remote regions (that have been less affected by admixture) diverged from the rest. Overall, we found the ability of the GNano system to differentiate self-declared Australian Aboriginal individuals was reasonable but had limitations that need to be recognised if these assignments are applied to unknown individuals.


Assuntos
Genética Populacional , Técnicas de Genotipagem/métodos , Grupo com Ancestrais Oceânicos/genética , Polimorfismo de Nucleotídeo Único , Austrália , Cromossomos Humanos Y , Impressões Digitais de DNA , Grupo com Ancestrais do Continente Europeu/genética , Marcadores Genéticos , Humanos , Repetições de Microssatélites , Filogenia , Análise de Componente Principal
16.
Medicine (Baltimore) ; 98(15): e15065, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30985656

RESUMO

Extensive coronary calcification without significant stenosis, described as calcific coronary artery disease (CCAD) may cause abnormal myocardial perfusion and hence generalized ischemia. There is a discrepancy in the expression pattern of CCAD compared to the well-known atherosclerotic disease which raises questions about the exact pathophysiology of coronary calcification and whether there is a genetic etiology for it.In this pilot study we studied 3 candidate genes, ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1), ATP Binding Cassette Subfamily C Member 6 (ABCC6), and 5'-Nucleotidase Ecto (NT5E) involved in pyrophosphate (PPi) and inorganic phosphate (Pi) metabolism, which may predispose to coronary arterial or valvular calcification. We studied 70 patients with calcific cardiac disease; 65 with CCAD (age 43-83 years) and 5 with calcific aortic valve disease (CAVD) (age 76-82 years).Five DNA variants potentially affecting protein function were found in 6 patients. One variant is a known disease-causing mutation in the ABCC6 gene. Our findings support that disturbances in the PPi and Pi metabolism might influence the development of CCAD and CAVD. However, segregation in the families must first be performed to ascertain any damaging effect of these variants we have found.We report 4 new genetic variants potentially related to coronary calcification, through the disturbed Pi and PPi metabolism. The search for direct causative genetic variants in coronary artery and aortic valve calcification must be broadened with other genes particularly those involved with Pi and PPi metabolism.


Assuntos
5'-Nucleotidase/genética , Calcinose/genética , Variação Genética , Cardiopatias/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Diester Fosfórico Hidrolases/genética , Pirofosfatases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Proteínas Ligadas por GPI/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores Sexuais , Suécia , Rigidez Vascular/genética
17.
Front Biosci (Schol Ed) ; 11: 75-88, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30844737

RESUMO

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors and absence of amplification of human epidermal growth factor receptor (HER2). This disease has no approved treatment with a poor prognosis particularly in African-American (AA) as compared to European-American (EA) patients. Gene ontology analysis showed specific gene pathways that are differentially regulated and gene signatures that are differentially expressed in AA as compared to EA. Such differences might underlie the basis for the aggressive nature and poor prognosis of TNBC in AA patients. In-depth studies of these pathways and differential genetic signature might give significant clues to improve our understanding of tumor biology associated with AA TNBC to advance the prognosis and survival rates. Along with gene ontology analysis, we suggest that post-translational modifications (PTM) could also play a crucial role in the dismal survival rate of AA TNBC patients. Further investigations are necessary to explore this terrain of PTMs to identify the racially disparate burden in TNBC.


Assuntos
Disparidades nos Níveis de Saúde , Receptores de Progesterona/metabolismo , Neoplasias de Mama Triplo Negativas/etnologia , Afro-Americanos/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Fenótipo , Prognóstico , Receptor ErbB-2/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Microambiente Tumoral
18.
Front Biosci (Schol Ed) ; 11: 136-160, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30844741

RESUMO

African-American (AA) women are more likely to die from breast cancer (BC), at any age, compared to European-American women. Although breakthroughs in pre-clinical studies have resulted in potentially actionable targets in AA BC, drugs that were rationally designed for these targets have performed poorly in clinical trials. Challenges with interpatient and intratumoral heterogeneity, lack of drug sensitivity and specificity, suboptimal biomarker cut-offs, lack of drug response predictive biomarkers, drug side effects, high costs of drug development, and under-representation of AAs in clinical trials complicate the development of targeted therapies for AA BC patients. Accumulating evidence suggests that racial disparities exist in non-genetic risk factors that can alter genetic and epigenetic programs to promote breast tumorigenesis. Herein, we present a "roadmap" that addresses non-genetic risk factors that are suspected to contribute to the racial disparity in BC mortality. Increased targeting of these non-genetic risk factors may proffer a safer and more economical route to alleviating the racially disparate burden in BC.


Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Afro-Americanos/genética , Consumo de Bebidas Alcoólicas , Biomarcadores , Tamanho Corporal , Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Características Culturais , Diabetes Mellitus/etnologia , Diabetes Mellitus/genética , Escolaridade , Disruptores Endócrinos , Grupo com Ancestrais do Continente Europeu/genética , Medo , Feminino , Disparidades nos Níveis de Saúde , Terapia de Reposição Hormonal , Humanos , Hipertensão/complicações , Hipertensão/etnologia , Hipertensão/genética , Seguro Saúde , Estilo de Vida , Menarca , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/etnologia , Obesidade/genética , Religião , Características de Residência , Fatores de Risco , Sono , Estresse Psicológico , Transportes
19.
Front Biosci (Schol Ed) ; 11: 178-192, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30844743

RESUMO

Growing evidence now links circadian disruption (CD) to increased risk of developing multiple types of cancer, including breast cancer (BC). In the US, African-American (AA) BC patients have a higher mortality rate than European-Americans (EAs) with BC, and a prime suspect in this racially disparate burden has been the greater incidence of an aggressive and highly heterogeneous BC subtype called triple-negative BC (TNBC), among AAs. AAs are also more prone to CD as larger proportions of AAs engage in night shift work than EAs, and the chronotype of AAs makes it harder for them to adapt to CD than EAs. Although clock gene dysregulation has been shown to perturb transactivation of key cell cycle and apoptosis regulators, little is known about how clock gene mis-expression affects TNBC outcomes. This review examines the prognostic value of clock genes in TNBC, and evaluates patterns of clock gene dysregulation in the individual TNBC molecular subtypes. Better understanding of how CD contributes to TNBC biology may illuminate new paths to improving disease outcomes and reducing BC-related racial disparities.


Assuntos
Relógios Circadianos , Neoplasias de Mama Triplo Negativas/genética , Afro-Americanos/genética , Ciclo Celular , Grupos Étnicos , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Perfilação da Expressão Gênica , Disparidades nos Níveis de Saúde , Humanos , Incidência , Prognóstico , Fatores de Risco , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/epidemiologia , Tolerância ao Trabalho Programado
20.
Med Sci Monit ; 25: 1917-1927, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30867406

RESUMO

BACKGROUND Numerous studies have been conducted on whether CD28 rs3116496 polymorphism affected cancer susceptibility, and these findings have been controversial. Thus, the purpose of this study was to assess the relationship between rs3116496 and susceptibility to cancer. MATERIAL AND METHODS The research published as of October 25, 2018 were comprehensively searched in PubMed, Embase, Cochrane Library and Chinese Wanfang database, CNKI, CBM. Statistical calculations performed using Stata12.0. RESULTS Overall analyses found that rs3116496 was a risk factor for cancer (C versus T, OR=1.14, 95% CI: 1.01-1.29, PH=0.003), and the heterogeneity was moderate (I²=53.3%). In subgroup analysis results by cancer types, the analysis showed that rs3116496 was a risk factor for breast cancer and leukemia. In the subgroup analysis by ethnicity, rs3116496 was a risk factor for cancer in the Asian population. After PHWE<0.05 was deleted, the analysis showed that rs3116496 might be related to the increased risk of colorectal cancer. CONCLUSIONS Our meta-analysis confirmed that rs3116496 was significantly related to cancer risk, especially in an Asian population, and was strongly correlated with the increased risk of breast cancer, leukemia and colorectal cancer.


Assuntos
Antígenos CD28/genética , Neoplasias/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Antígenos CD28/fisiologia , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
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