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1.
Am J Hum Genet ; 107(3): 379-380, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32888506

RESUMO

It is imperative for participation in genetics and genomics research to reflect humanity's diversity so that all people can enjoy its benefits. This will take a concerted effort by the research community and must include greater engagement with individuals and communities underrepresented in research. In engaging with vulnerable populations, it is essential that researchers guard against harm resulting from their participation.


Assuntos
Pesquisa Biomédica , Variação Genética/genética , Populações Vulneráveis , Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Europeu/genética , Genoma Humano , Genômica , Genética Humana , Humanos
3.
Medicine (Baltimore) ; 99(35): e21558, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871871

RESUMO

BACKGROUND: As indicated by numerous studies, there exists a relationship between the polymorphism of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to diabetic nephropathy (DN) in various populations; nonetheless, the findings remain inconsistent. Therefore, we carried out a meta-analysis to determine the relationship between the MTHFR gene polymorphism and DN susceptibility. MATERIALS AND METHOD: Related studies were identified from PubMed, Cochrane Library, EMBASE, and the China National Knowledge Infrastructure database (time period: from building the library to October 2019). The strength of the association was examined using odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: The findings illustrated that the C677T gene polymorphism was significantly associated with an enhanced susceptibility to DN compared to that with diabetes mellitus in allelic (OR = 1.64, 95% CI = 1.34-2.00, P < .001), dominant (OR = 1.85, 95% CI = 1.40-2.46, P < .001), codominant (heterozygote: OR = 1.67, 95% CI = 1.27-2.21, P < .001; homozygote: OR = 2.55, 95% CI = 1.82-3.57, P < .001), and recessive (OR = 1.89, 95% CI = 1.50-2.38, P < .001) models of the overall population. Moreover, as compared with the healthy controls, a significantly augmented susceptibility to DN was found in all 5 genetic comparison models (allelic: OR = 2.06, 95% CI = 1.58-2.67, P < .001; dominant: OR = 2.52, 95% CI = 1.73-3.69, P < .001; codominant: OR = 3.78, 95% CI = 2.50-5.70, P < .001; recessive: OR = 2.41, 95% CI = 1.96-2.97, P < .001). Furthermore, stratifying data by ethnicity revealed substantially augmented vulnerability to DN in not only Caucasian but also Asian populations. CONCLUSION: The present study suggests that the C677T polymorphism was associated with an augmented susceptibility to DN.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/epidemiologia , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/genética , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Humanos , Fatores de Risco
4.
Nat Commun ; 11(1): 4556, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917883

RESUMO

Previous genetic studies have identified local population structure within the Netherlands; however their resolution is limited by use of unlinked markers and absence of external reference data. Here we apply advanced haplotype sharing methods (ChromoPainter/fineSTRUCTURE) to study fine-grained population genetic structure and demographic change across the Netherlands using genome-wide single nucleotide polymorphism data (1,626 individuals) with associated geography (1,422 individuals). We identify 40 haplotypic clusters exhibiting strong north/south variation and fine-scale differentiation within provinces. Clustering is tied to country-wide ancestry gradients from neighbouring lands and to locally restricted gene flow across major Dutch rivers. North-south structure is temporally stable, with west-east differentiation more transient, potentially influenced by migrations during the middle ages. Despite superexponential population growth, regional demographic estimates reveal population crashes contemporaneous with the Black Death. Within Dutch and international data, GWAS incorporating fine-grained haplotypic covariates are less confounded than standard methods.


Assuntos
Grupos Étnicos/genética , Genética Populacional , Estudo de Associação Genômica Ampla , Estudos de Casos e Controles , Análise por Conglomerados , Emigração e Imigração , Grupo com Ancestrais do Continente Europeu/genética , Fluxo Gênico , Variação Genética/genética , Genoma , Geografia , Haplótipos , Humanos , Pessoa de Meia-Idade , Modelos Genéticos , Países Baixos , Polimorfismo de Nucleotídeo Único
5.
PLoS One ; 15(9): e0238255, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32936832

RESUMO

It was shown that the human Angiotensin-converting enzyme 2 (ACE2) is the receptor of recent coronavirus SARS-CoV-2, and variation in this gene may affect the susceptibility of a population. Therefore, we have analysed the sequence data of ACE2 among 393 samples worldwide, focusing on South Asia. Genetically, South Asians are more related to West Eurasian populations rather than to East Eurasians. In the present analyses of ACE2, we observed that the majority of South Asian haplotypes are closer to East Eurasians rather than to West Eurasians. The phylogenetic analysis suggested that the South Asian haplotypes shared with East Eurasians involved two unique event polymorphisms (rs4646120 and rs2285666). In contrast with the European/American populations, both of the SNPs have largely similar frequencies for East Eurasians and South Asians, Therefore, it is likely that among the South Asians, host susceptibility to the novel coronavirus SARS-CoV-2 will be more similar to that of East Eurasians rather than to that of Europeans.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Infecções por Coronavirus/genética , Peptidil Dipeptidase A/genética , Pneumonia Viral/genética , Polimorfismo de Nucleotídeo Único , Receptores Virais/genética , Ásia/epidemiologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/etnologia , Grupo com Ancestrais do Continente Europeu/genética , Haplótipos/genética , Migração Humana , Humanos , Desequilíbrio de Ligação , Pandemias , Filogenia , Pneumonia Viral/etnologia
6.
Nat Commun ; 11(1): 4423, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887889

RESUMO

Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.


Assuntos
Carcinogênese/genética , Neoplasias/genética , Adulto , Idoso , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Pleiotropia Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco
8.
PLoS Genet ; 16(8): e1008896, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32853200

RESUMO

Identifying regions of positive selection in genomic data remains a challenge in population genetics. Most current approaches rely on comparing values of summary statistics calculated in windows. We present an approach termed SURFDAWave, which translates measures of genetic diversity calculated in genomic windows to functional data. By transforming our discrete data points to be outputs of continuous functions defined over genomic space, we are able to learn the features of these functions that signify selection. This enables us to confidently identify complex modes of natural selection, including adaptive introgression. We are also able to predict important selection parameters that are responsible for shaping the inferred selection events. By applying our model to human population-genomic data, we recapitulate previously identified regions of selective sweeps, such as OCA2 in Europeans, and predict that its beneficial mutation reached a frequency of 0.02 before it swept 1,802 generations ago, a time when humans were relatively new to Europe. In addition, we identify BNC2 in Europeans as a target of adaptive introgression, and predict that it harbors a beneficial mutation that arose in an archaic human population that split from modern humans within the hypothesized modern human-Neanderthal divergence range.


Assuntos
Grupo com Ancestrais do Continente Europeu/genética , Modelos Genéticos , Taxa de Mutação , Animais , Proteínas de Ligação a DNA/genética , Variação Genética , Humanos , Proteínas de Membrana Transportadoras , Homem de Neandertal/genética , Seleção Genética , Software
9.
Medicine (Baltimore) ; 99(31): e21479, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756173

RESUMO

BACKGROUND: To comprehensively evaluate the association between the polymorphism of matrix metalloproteinase-9 (MMP-9)-C1562T (rs3918242) and susceptibility to chronic obstructive pulmonary disease (COPD) in middle-aged and elderly patients through Meta-analysis. METHODS: PubMed, EMBASE, CNKI, Wanfang, VIP, and other databases were searched by computer in the inception to August 2019 to collect all the case-control studies that met the inclusion criteria in this literature. Meta-analysis was performed using Stata 15.0, including the OR value calculations of the association between the merged MMP-9-C1562T polymorphism and the COPD susceptibility. Subgroup analysis, sensitivity analysis, and publication bias test were also performed. A total of 13 literature were included in this Meta-analysis with a total of 2512 cases and 2716 controls. RESULTS: The results have shown that the OR of MMP-9-C1562T T allele to C allele was 0.35 (95% confidence interval [CI]: 0.23-0.52, P < .01). The subgroup analysis of ethnicity result showed that the merged OR of MMP-9-C1562T T allele to C allele was 0.24 (95% CI: 0.17-0.34, P < .01) in Caucasian while the merged OR was 0.62 (95% CI: 0.22-1.70, P > .05) in Asian. However, there were no statistically significant models in the dominant, recessive, homozygote and heterozygote genetic models. CONCLUSION: The MMP-9-C1562T polymorphism was associated with the susceptibility to middle-aged and elderly COPD patients. Compared with T allele, C allele increased the risk of disease, especially in Caucasian, but not found in Asian.


Assuntos
Predisposição Genética para Doença/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
10.
PLoS Med ; 17(7): e1003178, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32701947

RESUMO

BACKGROUND: Smoking is a well-established cause of lung cancer and there is strong evidence that smoking also increases the risk of several other cancers. Alcohol consumption has been inconsistently associated with cancer risk in observational studies. This mendelian randomisation (MR) study sought to investigate associations in support of a causal relationship between smoking and alcohol consumption and 19 site-specific cancers. METHODS AND FINDINGS: We used summary-level data for genetic variants associated with smoking initiation (ever smoked regularly) and alcohol consumption, and the corresponding associations with lung, breast, ovarian, and prostate cancer from genome-wide association studies consortia, including participants of European ancestry. We additionally estimated genetic associations with 19 site-specific cancers among 367,643 individuals of European descent in UK Biobank who were 37 to 73 years of age when recruited from 2006 to 2010. Associations were considered statistically significant at a Bonferroni corrected p-value below 0.0013. Genetic predisposition to smoking initiation was associated with statistically significant higher odds of lung cancer in the International Lung Cancer Consortium (odds ratio [OR] 1.80; 95% confidence interval [CI] 1.59-2.03; p = 2.26 × 10-21) and UK Biobank (OR 2.26; 95% CI 1.92-2.65; p = 1.17 × 10-22). Additionally, genetic predisposition to smoking was associated with statistically significant higher odds of cancer of the oesophagus (OR 1.83; 95% CI 1.34-2.49; p = 1.31 × 10-4), cervix (OR 1.55; 95% CI 1.27-1.88; p = 1.24 × 10-5), and bladder (OR 1.40; 95% CI 1.92-2.65; p = 9.40 × 10-5) and with statistically nonsignificant higher odds of head and neck (OR 1.40; 95% CI 1.13-1.74; p = 0.002) and stomach cancer (OR 1.46; 95% CI 1.05-2.03; p = 0.024). In contrast, there was an inverse association between genetic predisposition to smoking and prostate cancer in the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium (OR 0.90; 95% CI 0.83-0.98; p = 0.011) and in UK Biobank (OR 0.90; 95% CI 0.80-1.02; p = 0.104), but the associations did not reach statistical significance. We found no statistically significant association between genetically predicted alcohol consumption and overall cancer (n = 75,037 cases; OR 0.95; 95% CI 0.84-1.07; p = 0.376). Genetically predicted alcohol consumption was statistically significantly associated with lung cancer in the International Lung Cancer Consortium (OR 1.94; 95% CI 1.41-2.68; p = 4.68 × 10-5) but not in UK Biobank (OR 1.12; 95% CI 0.65-1.93; p = 0.686). There was no statistically significant association between alcohol consumption and any other site-specific cancer. The main limitation of this study is that precision was low in some analyses, particularly for analyses of alcohol consumption and site-specific cancers. CONCLUSIONS: Our findings support the well-established relationship between smoking and lung cancer and suggest that smoking may also be a risk factor for cancer of the head and neck, oesophagus, stomach, cervix, and bladder. We found no evidence supporting a relationship between alcohol consumption and overall or site-specific cancer risk.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Análise da Randomização Mendeliana/métodos , Neoplasias/etiologia , Fumar/genética , Bancos de Espécimes Biológicos , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Reino Unido
11.
PLoS One ; 15(7): e0236402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32701999

RESUMO

BACKGROUND: Endometrial cancer (EC) mortality is particularly high among non-Hispanic Blacks and is twice that of non-Hispanic Whites. However, comparisons of EC survival outcomes by race/ethnicity are often confounded by histology and grade. Here, we analyze EC survival disparities in multiracial Florida with a focus on EC types (1 and 2) and subtypes, defined according to histology and grade. METHODS: All 27,809 cases of EC diagnosed during 2005-2016 were obtained from the Florida Cancer Registry. Age-standardized, 5-year cause-specific survival by race/ethnicity and histological type were calculated. Fine and Gray competing risk regression was used to estimate sub-distribution hazard ratios (sHRs) for associations between risk of death due to EC and potential predictive factors such as histology/grade, age, stage at diagnosis, and insurance. RESULTS: Type 2 EC accounted for only 38.7% of all incident EC-cases but 74.6% of all EC-deaths. Blacks were disproportionately affected by type 2 EC (57.6%) compared to Whites, Hispanics, and Asians (35.6%, 37.7%, and 43.0%, respectively). Age-adjusted 5-year survival for types 1 and 2 were 85.3% and 51.6%, respectively; however, there was wide variation within type 2 subtypes, ranging from 60.2% for mixed cell EC to as low as 30.1% for carcinosarcoma. In the multivariable model, Blacks with type 2 EC had a 23% higher risk of death due to EC (sHR: 1.23, 95%CI: 1.12-1.36) compared to Whites. CONCLUSIONS: Population-based analyses should consider the histological heterogeneity of EC because the less common type 2 EC drives racial/ethnic survival disparities in EC. Black women have a higher proportion of more aggressive histological types and an overall higher risk of death due to EC than Whites. To the extent that some of these histological types may be considered different diseases and require specific treatment approaches, further research on etiology and prognosis for detailed type 2 EC subtypes is warranted.


Assuntos
Sobreviventes de Câncer , Neoplasias do Endométrio/epidemiologia , Endométrio/patologia , Neoplasias Uterinas/epidemiologia , Adolescente , Adulto , Afro-Americanos/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Intervalo Livre de Doença , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Florida/epidemiologia , Disparidades nos Níveis de Saúde , Hispano-Americanos/genética , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , Adulto Jovem
12.
Prostate ; 80(13): 1045-1057, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32687658

RESUMO

BACKGROUND: There is a need to develop novel therapies which could be beneficial to patients with prostate cancer (CaP) including those who are predisposed to poor outcome, such as African-Americans. This study investigates the role of ROBO1-pathway in predicting outcome and race-based disparity in patients with CaP. METHODS AND RESULTS: Aided by RNA sequencing-based DECIPHER-testing and immunohistochemical (IHC) analysis of tumors we show that ROBO1 is lost during the progressive stages of CaP, a prevalent feature in African-Americans. We show that the loss of ROBO1 predicts high-risk of recurrence, metastasis and poor outcome of androgen-deprivation therapy in radical prostatectomy-treated patients. These data identified an aggressive ROBO1deficient /DOCK1+ve sub-class of CaP. Combined genetic and IHC data showed that ROBO1 loss is accompanied by DOCK1/Rac1 elevation in grade-III/IV primary-tumors and Mets. We observed that the hypermethylation of ROBO1-promoter contributes to loss of expression that is highly prevalent in African-Americans. Because of limitations in restoring ROBO1 function, we asked if targeting the DOCK1 could be an ideal strategy to inhibit progression or treat ROBO1deficient metastatic-CaP. We tested the pharmacological efficacy of CPYPP, a selective inhibitor of DOCK1 under in vitro and in vivo conditions. Using ROBO1-ve and ROBO1+ve CaP models, we determined the median effective concentration of CPYPP for growth. DOCK1-inhibitor treatment significantly decreased the (a) Rac1-GTP/ß-catenin activity, (b) transmigration of ROBO1deficient cells across endothelial lining, and (c) metastatic spread of ROBO1deficient cells through the vasculature of transgenicfl Zebrafish model. CONCLUSION: We suggest that ROBO1 status forms as predictive biomarker of outcome in high-risk populations such as African-Americans and DOCK1-targeting therapy has a clinical potential for treating metastatic-CaP.


Assuntos
Afro-Americanos/genética , Proteínas do Tecido Nervoso/genética , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/genética , Receptores Imunológicos/genética , Proteínas rac de Ligação ao GTP/genética , Animais , Linhagem Celular Tumoral , Metilação de DNA , Grupo com Ancestrais do Continente Europeu/genética , Disparidades nos Níveis de Saúde , Humanos , Imuno-Histoquímica , Masculino , Metástase Neoplásica , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/deficiência , Regiões Promotoras Genéticas , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Receptores Imunológicos/biossíntese , Receptores Imunológicos/deficiência , Peixe-Zebra , Proteínas rac de Ligação ao GTP/antagonistas & inibidores , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
13.
PLoS One ; 15(7): e0235512, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614901

RESUMO

The autism spectrum disorder (ASD) is a complex disorder encompassing a broad phenotypic and genotypic variability. The short (S)/long (L) 5-HTTLPR polymorphism has a functional role in the regulation of extracellular serotonin levels and both alleles have been associated to ASD. Most studies including European, American, and Asian populations have suggested an ethnical heterogeneity of this polymorphism; however, the short/long frequencies from Latin American population have been under-studied in recent meta-analysis. Here, we evaluated the 5-HTTLPR polymorphism in Colombian individuals with idiopathic ASD and reported a non-preferential S or L transmission and a non-association with ASD risk or symptom severity. Moreover, to recognize the allelic frequencies of an under-represented population we also recovered genetic studies from Latin American individuals and compared these frequencies with frequencies from other ethnicities. Results from meta-analysis suggest that short/long frequencies in Latin American are similar to those reported in Caucasian population but different to African and Asian regions.


Assuntos
Transtorno do Espectro Autista/genética , Polimorfismo de Nucleotídeo Único , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Grupo com Ancestrais do Continente Asiático/genética , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/patologia , Grupo com Ancestrais do Continente Europeu/genética , Frequência do Gene , Genótipo , Humanos , América Latina , Índice de Gravidade de Doença
14.
PLoS One ; 15(7): e0233808, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673320

RESUMO

Similarly to other populations across the Americas, Argentinean populations trace back their genetic ancestry into African, European and Native American ancestors, reflecting a complex demographic history with multiple migration and admixture events in pre- and post-colonial times. However, little is known about the sub-continental origins of these three main ancestries. We present new high-throughput genotyping data for 87 admixed individuals across Argentina. This data was combined to previously published data for admixed individuals in the region and then compared to different reference panels specifically built to perform population structure analyses at a sub-continental level. Concerning the Native American ancestry, we could identify four Native American components segregating in modern Argentinean populations. Three of them are also found in modern South American populations and are specifically represented in Central Andes, Central Chile/Patagonia, and Subtropical and Tropical Forests geographic areas. The fourth component might be specific to the Central Western region of Argentina, and it is not well represented in any genomic data from the literature. As for the European and African ancestries, we confirmed previous results about origins from Southern Europe, Western and Central Western Africa, and we provide evidences for the presence of Northern European and Eastern African ancestries.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Europeu/genética , Genoma Humano , Índios Sul-Americanos/genética , Casamento , Linhagem , Grupo com Ancestrais do Continente Africano/etnologia , Argentina , Colonialismo , DNA/genética , Escravização , Grupo com Ancestrais do Continente Europeu/etnologia , Marcadores Genéticos , Variação Genética , Genética Populacional , Genótipo , Migração Humana , Humanos , Índios Sul-Americanos/etnologia , Modelos Genéticos
16.
Genes (Basel) ; 11(7)2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32635188

RESUMO

Angiotensin-converting enzyme 2 (ACE2) has been recognized as the entry receptor of the novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Structural and sequence variants in ACE2 gene may affect its expression in different tissues and determine a differential response to SARS-Cov-2 infection and the COVID-19-related phenotype. The present study investigated the genetic variability of ACE2 in terms of single nucleotide variants (SNVs), copy number variations (CNVs), and expression quantitative loci (eQTLs) in a cohort of 268 individuals representative of the general Italian population. The analysis identified five SNVs (rs35803318, rs41303171, rs774469453, rs773676270, and rs2285666) in the Italian cohort. Of them, rs35803318 and rs2285666 displayed a significant different frequency distribution in the Italian population with respect to worldwide population. The eQTLs analysis located in and targeting ACE2 revealed a high distribution of eQTL variants in different brain tissues, suggesting a possible link between ACE2 genetic variability and the neurological complications in patients with COVID-19. Further research is needed to clarify the possible relationship between ACE2 expression and the susceptibility to neurological complications in patients with COVID-19. In fact, patients at higher risk of neurological involvement may need different monitoring and treatment strategies in order to prevent severe, permanent brain injury.


Assuntos
Infecções por Coronavirus/patologia , Grupo com Ancestrais do Continente Europeu/genética , Variação Genética , Doenças do Sistema Nervoso/complicações , Peptidil Dipeptidase A/genética , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , Encéfalo/metabolismo , Biologia Computacional/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Genótipo , Humanos , Itália , Doenças do Sistema Nervoso/patologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
17.
Gene ; 757: 144924, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32622992

RESUMO

OBJECTIVE: N-acetyltransferase 2 (NAT2) polymorphism could participate in the metabolism of carcinogens through regulating the activity of a series of critical enzymes. However, the effects of NAT2 polymorphism on bladder cancer (BCa) risk were still inconclusive. In order to illustrate whether NAT2 polymorphism may influence the susceptibility to BCa, we conducted this updated meta-analysis. MATERIALS AND METHODS: Databases including PubMed, Medline, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure(CNKI) were systematically retrieved and we applied MetaGenyo to perform final meta-analysis. Odds ratios (ORs) as well as 95% confidence intervals (CIs) were calculated and Bonferroni method was applied to correct the P-value for multiple comparisons. The registration of this study protocol is at PROSPERO and ID is CRD42019133957. RESULTS: Ultimately, 54 case-control studies were identified for final meta-analysis (13343 BCa cases and 18,586 controls). Overall analysis indicated that the slow genotype in NAT2 polymorphism was obviously associated with BCa risk (PBonferroni < 0.001). Subgroup analyses demonstrated that significant risk with the slow genotype was observed in Caucasians, Asians, smokers, non-exposed individuals, high grade bladder cancer (HGBC) patients and muscle-invasive bladder cancer (MIBC) patients. In addition, the intermediate NAT2 genotype was revealed to increase the BCa risk of Asians and transitional cell carcinoma (TCC) patients. However, no correlation was identified in Africans with the NAT2 polymorphism. CONCLUSIONS: The slow NAT2 genotype was identified to be the risk genotype for BCa. The intermediate genotype could serve as the candidate risk genotype. The gene-smoking interaction with NAT2 polymorphism might accelerate the tumor progression.


Assuntos
Arilamina N-Acetiltransferase/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Bexiga Urinária/genética , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Humanos , Fumar/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/etnologia
18.
Gene ; 757: 144940, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32640303

RESUMO

OBJECTIVE: We sought to analyze the association between miR-146a rs2910164 G > C polymorphism and susceptibility to lung cancer using a meta-analysis of case-control studies. METHODS: We systematically searched for studies reporting on the relationship between miR-146a rs2910164 polymorphism and the risk of lung cancer in PubMed, Embase, Web of Science and Chinese National Knowledge Infrastructure databases. We then calculated pooled odds ratios (ORs), at 95% confidence interval (CI) to assess the aforementioned relationship. All the data were analyzed using statistical packages implemented in R version 3.6.2 (R Project for Statistical Computing), run in RStudio version 1.2.5033. RESULTS: A total of fifteen studies, comprising 6506 cases and 6576 controls, were enrolled in this meta-analysis. Significant associations were observed between miR-146a rs2910164 polymorphism and the risk of lung cancer based on overall pooled subjects under the allele, heterozygous, homozygous, dominant, and recessive genetic models (C vs. G: OR = 1.27, 95% CI: 1.12-1.44; GC vs. GG: OR = 1.23, 95% CI: 1.03-1.46; CC vs. GG: OR = 1.51, 95% CI: 1.18-1.93; GC + CC vs. GG: OR = 1.33, 95% CI: 1.10-1.61; CC vs. GG + GC: OR = 1.32, 95% CI: 1.13-1.53). Ethnicity-based subgroup analyses revealed no statistically significant differences in Asians using heterozygous and dominant genetic models. CONCLUSION: miR-146a rs2910164 G > C polymorphism may be a risk factor of lung cancer. Asian populations exhibiting heterozygous and dominant genotypes need to be further investigated to validate our findings.


Assuntos
Neoplasias Pulmonares/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Genes Dominantes , Heterozigoto , Humanos , Neoplasias Pulmonares/etnologia
19.
Medicine (Baltimore) ; 99(28): e21160, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664151

RESUMO

BACKGROUND: Previous studies have investigated the correlation between xeroderma pigmentosumcomplementation group C (XPC) variants and prostate adenocarcinoma (PA) risk. Nevertheless, research findings remain inconclusive. METHODS: We conducted a pooled analysis to obtain a more accurate estimation of the relationship on XPC exon15 Lys939Gln polymorphism with susceptibility to PA. Moreover, in silico tools were employed to investigate the effect of XPC expression on PA patients' survival time. RESULTS: A total of 4306 patients and 4779 control subjects were assessed. The overall results indicated that XPC Lys939Gln variant was associated with PA risk (recessive genetic model: odds ratio = 1.15, 95% confidence interval = 1.02-1.30, Pheterogeneity= .044, P = .021, I= 45.2), especially in Asian descendants. Population-based studies revealed similar results (odds ratio = 1.15, 95% confidence interval = 1.01-1.32, Pheterogeneity= .146, P = .040, I = 39.0). In silico tools showed that XPC expression in Caucasian patients was lower than in the normal group. No positive association was observed in African patients. PA subjects with high XPC expression had a longer overall survival time than low expression group. CONCLUSION: Our findings indicated that XPC Lys939Gln variant might contribute to increased PA susceptibility, especially for Asian patients.


Assuntos
Adenocarcinoma/genética , Proteínas de Ligação a DNA/genética , Éxons/genética , Predisposição Genética para Doença/genética , Neoplasias da Próstata/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de Risco
20.
Medicine (Baltimore) ; 99(29): e21045, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702845

RESUMO

BACKGROUND: Previous meta-analyses have explored the association between the C677T polymorphism of methyltetrahydrofolate reductase (MTHFR) and chronic kidney disease (CKD) but there were no studies with a decisive conclusion. Furthermore, the high heterogeneity among different populations is not yet interpreted. OBJECTIVES: This study used trial sequential analysis (TSA) to evaluate whether the nowadays conclusion supported by current cumulative samples. We also applied case-weighted meta-regression to explore the potential gene-environment interactions. METHODS: For the first stage of this study we conducted a case-control study involving 847 dialysis patients from 7 hemodialysis centers in Taipei during 2015 to 2018 and 755 normal controls from a health center in the Tri-Service General Hospital. The second stage combined the results from the first stage with previous studies. The previous studies were collected from PubMed, EMBASE, and Web of Science databases before January 2018. RESULTS: From the case-control study, the T allele of MTHFR C677T appeared to have a protective effect on end-stage renal disease compared with the C allele [odds ratio (OR): 0.80, 95% CI (confidence interval) = 0.69-0.93]. However, the meta-analysis contradicted the results in Asian (OR = 1.12, 95% CI = 0.96-1.30). The same analysis was also applied in Caucasian and presented similar results from Asian (OR = 1.18, 95% CI = 0.98-1.42). The TSA showed our case-control study to be the decisive sample leading to a null association among Asian population. The high heterogeneity (I = 75%) could explain the contradictory results between the case-control study and the meta-analysis. However, further case-weighted meta-regression did not find any significant interaction between measured factors and MTHFR C677T on CKD. CONCLUSIONS: High heterogeneities were found in both Caucasian and Asian, which caused the null relationship in meta-analysis while there were significant effects in individual studies. Future studies should further explore the high heterogeneity that might be hidden in unmeasured gene-environment interactions, to explain the diverse findings among different populations.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Masculino , Taiwan
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