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1.
Anticancer Res ; 40(1): 27-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892550

RESUMO

BACKGROUND/AIM: Even though prostate cancer (PCa) has good prognosis, there is a discrepancy in the risk among ethnic groups, with high morbidity in African American men. Single nucleotide polymorphisms (SNPs) in interleukin 10 (IL-10) have been associated with inflammation and cancer risk. We investigated the association of five SNPs in the IL-10 promoter with clinical features such as Gleason score and smoking. MATERIALS AND METHODS: A total of 413 DNA samples were obtained from a nested case-control study of African American males who were genotyped for 5 SNPs utilizing pyrosequencing. Multiple and binary logistic regression models were applied to analyze the clinical and genotypic data. RESULTS: rs12122923 and rs1800871 were associated with PCa risk. Smoking was also found to increase the risk of PCa by 1.6-fold. rs1800893 was found to be associated with lower grades for prostate cancer. CONCLUSION: IL-10 promoter polymorphisms might be a risk factor for PCa development in smoking subjects and PCa progression.


Assuntos
Afro-Americanos/genética , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Neoplasias da Próstata/etiologia , Fumar/efeitos adversos , Idoso , Alelos , Biomarcadores , Estudos de Casos e Controles , Suscetibilidade a Doenças , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Medição de Risco , Fatores de Risco
2.
Anticancer Res ; 39(11): 5861-5866, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704810

RESUMO

BACKGROUND: We hypothesized that ancestry-mediated methylated DNA changes may drive racial and ethnic disparity in prostate cancer (PCa). To test this hypothesis, we analyzed genetic ancestry and association with DNA methylation changes in PCa disparity. MATERIALS AND METHODS: Pyrosequencing and ancestry informative markers were used for DNA methylation and genetic ancestry testing, respectively. RESULTS: Using Spearman rho rank correlation test, the data demonstrated significant (p<0.05) and variable association between African-American ancestry and DNA methylation for all genes investigated in prostate tissues. CONCLUSION: Genetic ancestry influences DNA methylation and this modifying factor must be considered in epigenetic association studies in populations of admixed patients.


Assuntos
Afro-Americanos/genética , Biomarcadores Tumorais/genética , Metilação de DNA , Grupo com Ancestrais do Continente Europeu/genética , Regulação Neoplásica da Expressão Gênica , Disparidades em Assistência à Saúde , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
3.
Cancer Genomics Proteomics ; 16(4): 245-255, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31243105

RESUMO

BACKGROUND/AIM: Vitamin D receptor (VDR) is present in numerous cellular pathways and it has been suggested that VDR genetic variants influence individual susceptibility to prostate cancer. Also, analyses of single nucleotide polymorphisms (SNPs) in VDR revealed ethnicity-associated polymorphisms. The aim of this study was to identify VDR SNPs in African American men with and without prostate cancer. MATERIALS AND METHODS: The entire VDR gene was screened for germline mutations in a case-control study by denaturing high performance liquid chromatography and DNA sequencing. Logistic regression was used to estimate the association of SNPs, age, family history, and Gleason score with prostate cancer risk. RESULTS: Six SNPs in the non-coding regions, and one SNP in the coding region, were detected. SNP 1 (c.278-69G>A) and SNP 4 (c.907+75C>T) have not been previously reported. SNP 4 had a significant protective effect (ß=-0.6, p<0.05); whereas, SNP 7 (rs7975232) showed an increase association with prostate cancer risk and high Gleason score (ß=0.32, p<0.05). SNP 4, SNP 7 and age were better predictors of prostate cancer risk than family history with a high degree of sensitivity (74.7%) and specificity (92.4%). CONCLUSION: SNP 4 and SNP 7 could be promising markers for prediction of reduced or increased prostate cancer risk, respectively.


Assuntos
Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/genética , Receptores de Calcitriol/genética , Afro-Americanos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia
4.
PLoS One ; 13(9): e0203322, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30204798

RESUMO

The objective of this work was to investigate the clinical significance of promoter gene DNA methylation changes in whole blood from African-American (AA) men with prostate cancer (PCa). We used high throughput pyrosequencing analysis to quantify percentage DNA methylation levels in a panel of 8 genes (RARß2, TIMP3, SPARC, CDH13, HIN1, LINE1, CYB5R2 and DRD2) in blood DNA obtained from PCa and non-cancerous controls cases. Correlations of methylation status and various clinicopathological features were evaluated. Six genes tested achieved significant difference in DNA methylation levels between the PCa compared to control cases (P < 0.05). The TIMP3 loci demonstrated significant correlation of DNA methylation with age for all cases analyzed (p < 0.05). We observed an inverse correlation between CDH13 methylation (p = 0.045; r = -0.21) and serum vitamin D level whereas TIMP3 methylation (p = 0.021; r = -0.24) and DRD2 methylation (p = 0.056; r = -0.201) showed inverse correlation with supplementary vitamin D in the cancer cases. We also observed a direct correlation between methylation of RARß2 (p = 0.0036; r = 0.293) and SPARC (p = 0.0134; r = 0.20) loci with PSA level in the controls but not the cancer cases. In addition, alcohol cases significantly correlated with higher RARß2 methylation (p = 0.0314) in comparison with non-alcohol cases. Furthermore, we observed an inverse correlation of DRD2 methylation (p = 0.0349; r = -0.343) and Gleason score. Our data suggests that promoter methylation occurred more frequently in the blood of AA PCa and is associated with various clinicopathological features in AA men with PCa.


Assuntos
Afro-Americanos/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Metilação de DNA , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Adulto , Idoso , Caderinas/genética , Estudos de Casos e Controles , Citocinas/genética , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Osteonectina/genética , Regiões Promotoras Genéticas , Neoplasias da Próstata/patologia , Receptores de Dopamina D2/genética , Receptores do Ácido Retinoico/genética , Fatores de Risco , Inibidor Tecidual de Metaloproteinase-3/genética , Proteínas Supressoras de Tumor/genética , Vitamina D/sangue
5.
Stat Methods Med Res ; 27(9): 2641-2656, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30103662

RESUMO

We establish a zero-inflated (random-effects) logistic-Gaussian model for clustered binary data in which members of clusters in one latent class have a zero response with probability one, and members of clusters in a second latent class yield correlated outcomes. Response probabilities in terms of random-effects models are formulated, and maximum marginal likelihood estimation procedures based on Gaussian quadrature are developed. Application to esophageal cancer data in Chinese families is presented.


Assuntos
Análise por Conglomerados , Interpretação Estatística de Dados , Algoritmos , China , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etnologia , Feminino , Humanos , Masculino , Distribuição Normal , Distribuição de Poisson , Análise de Regressão
6.
Prostate ; 78(11): 801-811, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29682763

RESUMO

BACKGROUND: Although studies have observed several markers correlate with progression of prostate cancer (PCa), no specific markers have been identified that accurately predict the progression of this disease, even in African American (AA) men who are generally at higher risk than other ethnic groups. The primary goal of this study was to explore whether three markers could predict the progression of PCa. METHOD: We investigated protein expression of Annexin 2 (ANX2), serine peptidase inhibitor, kazal type 1(SPINK1)/tumor-associated trypsin inhibitor (TATI), and heat shock protein 60 (Hsp60) in 79 archival human prostate trans-rectal ultrasound (TRUS) biopsy tissues according to a modified World Health Organization (WHO) classification: normal (WHO1a), Gleason Score (GS6 (WHO1b), GS7 subgroups (WHO2 = 3 + 4, WHO3 = 4 + 3), GS8 (WHO4), and GS9-10 (WHO5). AA men aged 41-90 diagnosed from 1990 to 2013 at Howard University were included. Automated staining assessed expression of each biomarker. Spearman correlation assessed the direction and relationship between biomarkers, WHO and modified WHO GS, age, and 5-year survival. A two-tailed t-test and ANOVA evaluated biomarkers expression in relationship to WHO normal and other GS levels, and between WHO GS levels. A logistic and linear regression analysis examined the relationship between biomarker score and WHO GS categories. Kaplan-Meier curves graphed survival. RESULTS: ANX2 expression decreased monotonically with the progression of PCa while expression of SPINK1/TATI and Hsp60 increased but had a more WHO GS-specific effect; SPINK1/TATI differed between normal and GS 2-6 and HSP60 differed between GS 7 and GS 2-6. WHO GS was found to be significantly and negatively associated with ANX2, and positively with SPINK1/TATI and Hsp60 expression. High SPINK1/TATI expression together with the low ANX2 expression at higher GS exhibited a bi-directional relationship that is associated with PCa progression and survival. CONCLUSION: Importantly, the data reveal that ANX2, and SPINK1/TAT1 highly associate with WHO GS and with the transition from one stage of PrCa to the next in AA men. Future research is needed in biracial and larger population studies to confirm this dynamic relationship between ANX2 and SPINK1 as independent predictors of PCa progression in all men.


Assuntos
Afro-Americanos , Anexina A2/biossíntese , Chaperonina 60/biossíntese , Proteínas Mitocondriais/biossíntese , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/metabolismo , Inibidor da Tripsina Pancreática de Kazal/biossíntese , Estudos de Casos e Controles , Progressão da Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia
7.
Cancer Genomics Proteomics ; 14(6): 461-467, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29109096

RESUMO

BACKGROUND/AIM: Denaturing high-performance liquid chromatography (DHPLC) is a technique that is used to detect mutations. The aim of the present study was to determine whether DHPLC elution patterns of vitamin D receptor (VDR) gene PCR products can serve as indicators of susceptibility to prostate cancer (PCa) risk. MATERIALS AND METHODS: DNA samples of PCa cases and controls were screened for mutations and/or polymorphisms in coding exons of VDR gene using DHPLC analysis. Logistic regression, phi-coefficient (ϕ), and Backward Wald models were used to analyze the data. RESULTS: Similar elution patterns of exons 1, 6, 7 and 9 along with higher prevalence of heteroduplex DNA were observed in PCa samples than in controls. Exons 4 and 8 had highly significant protective effects (p<0.05). Whereas, exons 5, 7, and 9 were perfectly positively correlated with PCa risk (ϕ=1), thus presenting candidate exons significantly associated with susceptibility to PCa. CONCLUSION: DHPLC elution patterns of the selected exons could be useful to predict susceptibility to develop PCa.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Reação em Cadeia da Polimerase/métodos , Receptores de Calcitriol/genética , Adulto , Afro-Americanos , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
8.
Autoimmune Infect Dis ; 2(3)2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27559544

RESUMO

AIM: To examine the association of TLR4 Asp299Gly and MICA exon 5 microsatellites polymorphisms with severity of trachoma in a sub-Saharan East Africa population of Tanzanian villagers. METHODS: The samples were genotyped for MICA exon 5 microsatellites and the TLR4 299 A/G polymorphism by Restriction Fragment Length Polymorphism (RFLP), and GeneScan®, respectively. The association of TLR4 Asp299Gly and MICA exon 5 microsatellites with inflammatory trachoma (TI) and trichiasis (TI) were examined. RESULTS: The results showed an association between TLR4 and MICA polymorphisms and trachoma disease severity, as well as with protection. TLR4 an allele was significantly associated with inflammatory trachoma (p=0.0410), while the G allele (p=0.0410) was associated with protection. CONCLUSION: TLR4 and MICA may modulate the risk of severity to trachoma disease by modulating the immune response to Ct. In addition; the increased frequency of MICA-A9 heterozygote in controls may suggest a positive selection of these alleles in adaptation to environments where Ct is endemic.

9.
Appl Appl Math ; 11(1): 83-96, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28729894

RESUMO

The problem of incomplete data is a common phenomenon in research that involves the longitudinal design approach. We investigate and develop a likelihood-based approach for incomplete longitudinal binary data using the disposition model when the missing value mechanism is non-ignorable. We combined Markov's transition and a logistic regression model to build the dropout process and model the response using conditional logistic regression model. By holding the missingness parameter that is weakly identified constant, we analyzed their effects through a sensitivity analysis as the estimation of parameters in MLE for non-ignorable missing data is not generally plausible. An application of our approach to Schizophrenia clinical trial is presented.

10.
J Data Sci ; 14(2): 365-382, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28066502

RESUMO

Incomplete data are common phenomenon in research that adopts the longitudinal design approach. If incomplete observations are present in the longitudinal data structure, ignoring it could lead to bias in statistical inference and interpretation. We adopt the disposition model and extend it to the analysis of longitudinal binary outcomes in the presence of monotone incomplete data. The response variable is modeled using a conditional logistic regression model. The nonresponse mechanism is assumed ignorable and developed as a combination of Markov's transition and logistic regression model. MLE method is used for parameter estimation. Application of our approach to rheumatoid arthritis clinical trials is presented.

11.
In Vivo ; 28(6): 1181-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25398820

RESUMO

BACKGROUND/AIM: Vitamin D deficiency in African-Americans is common due to the high melanin content of the skin that reduces the absorption of UV radiation. To determine if there is a correlation between UV exposure, tanning potential and vitamin D with prostate cancer (PC) risk, we conducted a case-control study of 183 African-American men aged 40 years and older residing in the Washington, DC area. PATIENTS AND METHODS: PC status was described as a binary variable as the presence or absence of cancer and the environmental factors as continuous variables. We used a logistic regression model describing PC as the response, while age, tanning potential, sunlight and vitamin D were treated as the predictors. RESULTS: Men aged 60 years and older had a seven-fold increased risk for developing PC compared to those aged 50 years and less (p<0.003). Tanning potential was a significant (p=0.05) risk factor for PC, while sunlight exposure and vitamin D were not. Tanning potential was also significant (p=0.044) when adjusted for vitamin D and age. However, tanning potential was only marginally significant when adjusted for sunlight exposure (p=0.064) CONCLUSION: The findings of this study indicate that tanning potential may be a predictor for PC risk in African-American men.


Assuntos
Afro-Americanos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etiologia , Bronzeado , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Luz Solar , Raios Ultravioleta , Vitamina D/sangue , Vitamina D/metabolismo
12.
Clin Transl Sci ; 5(1): 60-4, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22376259

RESUMO

Single nucleotide polymorphisms (SNPs) in the promoter and untranslated region of cyclooxygenase (COX)-2, an inducible enzyme responsible for the synthesis of prostaglandins, have been reported to modulate the risk for many human cancers. We performed comprehensive linkage disequilibrium (LD) and haplotype analyses of 13 single nucleotide polymorphisms of the COX-2 gene and examined its susceptibility to adenoma development in 72 African American cases and 142 controls. Results revealed significant variation in LD patterns with consequence for adenoma development. Two distinct haplotype blocks were identified; one block covered the coding regions of exon 1, introns and a section of the 3'-unstranslated region (3'-UTR), whereas the second block resided solely in the 3'-UTR region. A haplotype in block 1 increased the risk of adenoma development by threefold (odds ratio [OR]= 2.9, confidence interval [CI]= 1.8-3.7, P= 0.002). Regression analysis showed, increase in copies of minor alleles of 6,064(T>C) polymorphism associated with increased odds of adenoma development by 80% (OR = 1.80, CI = 1.09-3.21, P= 0.034), 10,848(G>A) by 84% (OR = 1.84, CI = 1.05-3.23, P= 0.034) and 10,935(A>G) by 32% (OR = 1.32, CI = 1.12-3.69, P= 0.036). These results support the hypothesis that COX-2 gene might play a role in the etiology of colon cancer and warrant further investigation in other cancers. Besides, these variations should be taken into account for disease-based association studies in which the COX-2 polymorphism is considered as a candidate gene. Clin Trans Sci 2012; Volume 5: 60-64.


Assuntos
Adenoma/genética , Pólipos Adenomatosos/genética , Pólipos do Colo/genética , Neoplasias Colorretais/genética , Ciclo-Oxigenase 2/genética , Haplótipos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Regiões 3' não Traduzidas , Adenoma/enzimologia , Adenoma/etnologia , Adenoma/patologia , Pólipos Adenomatosos/enzimologia , Pólipos Adenomatosos/etnologia , Pólipos Adenomatosos/patologia , Adulto , Afro-Americanos/genética , Idoso , Estudos de Casos e Controles , Pólipos do Colo/enzimologia , Pólipos do Colo/etnologia , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/patologia , District of Columbia/epidemiologia , Éxons , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Íntrons , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Regiões Promotoras Genéticas , Medição de Risco , Fatores de Risco
13.
Clin Cancer Res ; 16(14): 3539-47, 2010 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-20606036

RESUMO

PURPOSE: Aberrant DNA methylation changes are common somatic alterations in prostate carcinogenesis. We examined the methylation status of six genes in prostate tissue specimens from African American (AA) and Caucasian (Cau) males. EXPERIMENTAL DESIGN: We used pyrosequencing to quantitatively measure the methylation status of GSTP1, AR, RARbeta2, SPARC, TIMP3, and NKX2-5. Real-time PCR was used to determine gene expression, and gene reactivation was analyzed by 5-aza-2'-deoxycytidine and/or trichostatin A treatment. RESULTS: Statistical analysis showed significantly higher methylation in the prostate cancer tissue samples in comparison with matched normal samples for GSTP1 (P = 0.0001 for AA; P = 0.0008 for Cau), RARbeta2 (P < 0.001 for AA and Cau), SPARC (P < 0.0001 for AA and Cau), TIMP3 (P < 0.0001 for AA and Cau), and NKX2-5 (P < 0.0001 for AA; P = 0.003 for Cau). Overall, we observed significant differences (P < 0.05) in the methylation level for all genes, except GSTP1, in the AA samples in comparison with the Cau samples. Furthermore, regression analysis revealed significantly higher methylation for NKX2-5 (P = 0.008) and TIMP3 (P = 0.039) in normal prostate tissue samples from AA in comparison with Cau, and a statistically significant association of methylation with age for NKX2-5 (P = 0.03) after adjusting for race. CONCLUSION: Our findings show higher methylation of several genes in prostate tissue samples from AA in comparison with Cau and may potentially contribute to the racial differences that are observed in prostate cancer pathogenesis.


Assuntos
Afro-Americanos/genética , Metilação de DNA , Grupo com Ancestrais do Continente Europeu/genética , Genes , Proteínas de Homeodomínio/genética , Próstata/metabolismo , Fatores de Transcrição/genética , Idoso , Linhagem Celular Tumoral , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Glutationa S-Transferase pi/genética , Saúde , Proteína Homeobox Nkx-2.5 , Humanos , Masculino , Pessoa de Meia-Idade , Osteonectina/genética , Próstata/citologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/genética , Receptores do Ácido Retinoico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Inibidor Tecidual de Metaloproteinase-3/genética
14.
Prostate ; 70(3): 262-9, 2010 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-19830784

RESUMO

BACKGROUND: African American men have the highest rates of prostate cancer worldwide, and immunogenetic studies suggest that people of African descent have increased susceptibility to diseases of inflammation. Since genetic susceptibility is an etiological factor in prostate cancer, we hypothesize that sequence variants in the promoter region of the CD14 gene that regulate inflammation may modify individual susceptibility to this disease. METHODS: The CD14 promoter was screened for single-nucleotide polymorphisms (SNPs) using dHPLC. One variant, -260 C>T (rs2569190), was genotyped via restriction digest in all study participants (264 cases and 188 controls). The association of disease status and the polymorphism was analyzed by unconditional logistic regression. Odds ratios with 95% confidence intervals were calculated, stratifying by ethnicity and adjusting for age. Two-sided P-values of < or =0.05 were considered as statistically significant. RESULTS: Eleven variants (four novel) were identified in the promoter region of CD14. A marginal association between the C genotypes (C/C + C/T) and prostate cancer was found (P = 0.07). When stratified by age, among men > or =55 years of age, the C genotypes were significantly associated with prostate cancer (P < 0.05). When stratified by self-reported ethnicity, African American males who had the C genotypes were at a higher risk for prostate cancer (P < 0.05). CONCLUSIONS: This is the first study to show an association between the C genotypes of the CD14 (-260) variant and prostate cancer which supports the hypothesis that genetic variation in the inflammatory process can contribute to prostate cancer susceptibility in African American men.


Assuntos
Afro-Americanos/genética , Receptores de Lipopolissacarídeos/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Doença Crônica , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Imunidade Inata/genética , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Regiões Promotoras Genéticas
15.
J Biomed Sci Eng ; 3(10): 977-985, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21804923

RESUMO

In recent times genetic network analysis has been found to be useful in the study of gene-gene interactions, and the study of gene-gene correlations is a special analysis of the network. There are many methods for this goal. Most of the existing methods model the relationship between each gene and the set of genes under study. These methods work well in applications, but there are often issues such as non-uniqueness of solution and/or computational difficulties, and interpretation of results. Here we study this problem from a different point of view: given a measure of pair wise gene-gene relationship, we use the technique of pattern image restoration to infer the optimal network pair wise relationships. In this method, the solution always exists and is unique, and the results are easy to interpret in the global sense and are computationally simple. The regulatory relationships among the genes are inferred according to the principle that neighboring genes tend to share some common features. The network is updated iteratively until convergence, each iteration monotonously reduces entropy and variance of the network, so the limit network represents the clearest picture of the regulatory relationships among the genes provided by the data and recoverable by the model. The method is illustrated with a simulated data and applied to real data sets.

16.
Trans Am Clin Climatol Assoc ; 120: 429-34, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19768195

RESUMO

BACKGROUND: Howard University Hospital (HUH) is the first hospital in the nation to have instituted a hospital-wide routine rapid HIV screening campaign as recommended by the CDC for healthcare settings. METHODS: HUH developed a protocol and implemented a hospital-wide routine HIV screening in October 2006. Rapid oral fluid-based HIV testing was conducted throughout the hospital using the OraSure OraQuick Advance Rapid HIV-1/2 Antibody Test. Patients with a preliminarily reactive test result were either referred for confirmatory testing or offered a Western Blot confirmatory test on-site and referred for follow-up care. This is a report on the progress of this program for the first eight months. RESULTS: Of the 9,817 patients offered HIV testing, 5,642 consented. The mean age of the screened population was 40.7 years. Ninety percent of the patients screened were black and 55% were female. A preliminarily reactive test result was identified in 139 patients for a seroprevalence rate of 2.46%. Of these patients, 136, or 98% were black; 63% were male and 37% were female. HIV prevalence in the overall sample, among blacks, and among both black males and females peaked in the 40-54 year old age group. Challenges were experienced initially in securing confirmatory tests. CONCLUSIONS: Hospital-wide routine HIV screening is both possible and productive. The routine HIV screening campaign instituted at Howard University Hospital has identified a significant number of previously unidentified HIV positive persons. Success in assuring confirmatory testing and transition to care improved as time progressed.


Assuntos
Infecções por HIV/prevenção & controle , Hospitais Universitários , Programas de Rastreamento/métodos , Sorodiagnóstico da AIDS , Adolescente , Adulto , District of Columbia/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Programas de Rastreamento/tendências , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
17.
Invest Ophthalmol Vis Sci ; 50(4): 1734-8, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18824733

RESUMO

PURPOSE: Trachoma remains the leading preventable infectious cause of blindness in developing countries. Human leukocyte antigen (HLA) associations with ocular disease severity and persistent Chlamydia trachomatis infection of Tanzanians living in trachoma-endemic villages were examined to determine possible protective candidate allotypes for vaccine development. METHODS: Buccal swab scrapes were taken from subjects in the Trichiasis Study Group (TSG), which studied females only, and the Family Trachoma Study (FTS), which compared persistently infected probands who had severe disease with disease-free siblings and parents. DNA was purified for polymerase chain reaction sequence-specific oligonucleotide identification of HLA-DRB1, DQB1, and B allotypes. Infection was detected from conjunctival scrapes using a C. trachomatis-specific PCR-enzyme immunoassay for the MOMP-1 gene. RESULTS: In the TSG, DR*B11 (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.90; P=0.02) was significantly associated with lack of trichiasis, whereas HLA-B*07 (OR, 3.26; 95% CI, 1.42-7.49; P=0.004) and HLA-B*08 (OR, 5.12; 95% CI, 1.74-15.05; P=0.001) were associated with trichiasis. In addition, HLA-B*14 was significantly associated with inflammatory trachoma + follicular trachoma (OR, 3.76; 95% CI, 1.70-8.33; P=0.04). There were no significant allele frequencies for the FTS. CONCLUSIONS: The data suggest that HLA-DRB*11 may offer protection from trichiasis in trachoma hyperendemic villages. Complete allotype identification and designation of its respective protective CD4(+) T-cell antigens could provide a testable candidate vaccine for blindness prevention. Additionally, buccal swab DNA was sufficiently stable when acquired under harsh field conditions and stored long term in the freezer for low-resolution HLA typing.


Assuntos
Alelos , Doenças Endêmicas , Antígenos HLA-B/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Tracoma/genética , Tracoma/prevenção & controle , Adolescente , Adulto , Chlamydia trachomatis/patogenicidade , DNA Bacteriano/análise , Feminino , Citometria de Fluxo , Frequência do Gene , Genótipo , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Teste de Histocompatibilidade , Humanos , Mucosa Bucal , Hibridização de Ácido Nucleico , Porinas/genética , População Rural , Tanzânia/epidemiologia , Tracoma/epidemiologia
18.
Genet Epidemiol ; 31 Suppl 1: S34-42, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18046758

RESUMO

Group 4 at Genetic Analysis Workshop 15 focused on methods that exploited both linkage and association information to map disease loci. All contributions considered the dichotomous trait of rheumatoid arthritis, using either affected sibpairs and/or unrelated controls. While one contribution investigated linkage and association approaches separately in genome-wide analyses, the remaining others focused on joint linkage and association methods in specific genomic regions. The latter contributions proposed new methods and/or examined existing methods that addressed whether one or more polymorphisms partially or fully explained a linkage signal, particularly the methods proposed by Li et al. that are implemented in the computer program Linkage and Association Modeling in Pedigrees (LAMP). Using simulated SNP data under linkage peaks, several contributions found that existing family-based association approaches such as those of Martin et al. and Lake et al. had power similar to LAMP and to several methods proposed by the contributors for testing that a single nucleotide polymorphism partially explains a linkage peak. In evaluating methods for identifying if a polymorphism or a set of polymorphisms fully accounted for a linkage signal, several contributions found that it was important to understand that these methods may be subject to low power in some situations and thus, a non-significant result was not necessarily indicative of the polymorphism(s) being fully responsible for the linkage signal. Finally, modeling the disease using association evidence conditional on linkage may improve understanding of the etiology of disease.


Assuntos
Artrite Reumatoide/genética , Ligação Genética , Modelos Genéticos , Mapeamento Cromossômico , Feminino , Humanos , Masculino , Linhagem , Polimorfismo Genético
19.
Hum Genet ; 122(1): 83-94, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17530290

RESUMO

Association studies for complex diseases based on pedigree haplotype or genotype data have received increasing attention in the last few years. The similarity tests are appealing for these studies because they take into account of the DNA structure, but they have blind areas on which significant association can not be detected. Recently, we developed a dissimilarity method for this problem based on independent haplotype data, which eliminates the blind areas of the existing methods. As DNA collected on families are common in practice, and the data are either of the form of genotype or haplotype. Here we extend our method for association study to data on families. It can be used to evaluate different designs in terms of power. Simulation studies confirmed that the extended method improves the type I error rate and power. Applying this method to the Genetic Analysis Workshop 14 alcoholism data, we find that markers rs716581, rs1017418, rs1332184 and rs1943418 on chromosomes 1, 2, 9 and 18 yield strong signal (with P value 0.001 or lower) for association with alcoholism. Our work can serve as a guide in the design of association studies in families.


Assuntos
Família , Ligação Genética , Testes Genéticos/métodos , Genética Populacional/métodos , Desequilíbrio de Ligação , Polimorfismo Genético , Alcoolismo/genética , Sequência de Bases , Simulação por Computador , Frequência do Gene , Ligação Genética/fisiologia , Haplótipos , Humanos , Padrões de Herança , Modelos Genéticos
20.
Hum Genet ; 120(2): 253-61, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16807758

RESUMO

Association studies for complex diseases based on haplotype data have received increasing attention in the last few years. A commonly used nonparametric method, which takes haplotype structure into consideration, is to use the U-statistic to compare the similarities between genetic compositions in the case and control populations. Although the method and its variants are convenient to use in practice, there are some areas where the tests cannot detect even large differences between cases and controls. To overcome this problem and enhance the power, we propose a new form of the weighted U-statistic, which directly compares the dissimilarity between the haplotype structures in the case and control populations. We show that this test statistic is asymptotically a linear combination of the absolute values of normal random variables under the null hypothesis, and shifts strictly toward the right under the alternative, and therefore has no blind areas of detection. Simulation studies indicate that our test statistic overcomes the weakness of the existing ones and is robust and powerful as well.


Assuntos
Predisposição Genética para Doença , Haplótipos , Funções Verossimilhança , Sequência de Bases , Estudos de Casos e Controles , Simulação por Computador , Humanos , Estatísticas não Paramétricas
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