6 results on '"O'BRIEN, STEPHEN J."'
Search Results
2. The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove.
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Minzhong Tang, Lautenberger, James A., Xiaojiang Gao, Sezgin, Efe, Hendrickson, Sher L., Troyer, Jennifer L., David, Victor A., Li Guan, Mcintosh, Carl E., Xiuchan Guo, Yuming Zheng, Jian Liao, Hong Deng, Malasky, Michael, Kessing, Bailey, Winkler, Cheryl A., Carrington, Mary, dé The, Guy, Yi Zeng, and O'Brien, Stephen J.
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NASOPHARYNX cancer , *MAJOR histocompatibility complex , *HLA histocompatibility antigens , *EPSTEIN-Barr virus diseases - Abstract
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA -B, and HLA -C class I genes (PHLA-A-aa-site-62 = 7.4 x10-29; PHLA-B-aa-site-116 = 6.56x10 ;PHLA-C-aa-site-156 = 6.8x10-8 respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China. [ABSTRACT FROM AUTHOR]
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- 2012
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3. Genetic Polymorphisms of CYP2E1, GSTP1, NQO1 and MPO and the Risk of Nasopharyngeal Carcinoma in a Han Chinese Populationof Southern China.
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Xiuchan Guo, Yi Zeng, Hong Deng, Jian Liao, Yuming Zheng, Ji Li, Kessing, Bailey, and O'Brien, Stephen J.
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GENETIC research , *GENETIC polymorphisms , *POPULATION genetics , *HEREDITY , *STATISTICAL hypothesis testing , *BIOCHEMISTRY , *OPEN learning , *NUCLEOTIDES - Abstract
Background: Southern China is a major area for endemic nasopharyngeal carcinoma (NPC). Genetic factors as well as environmental factors play a role in development of NPC. To investigate the roles of previously described carcinogen metabolism gene variants for NPC susceptibility in a Han Chinese population, we conducted a casecontrol study in two independent study population groups afflicted with NPC in Guangdong and Guangxi Provinces of southern China. Methods: Five single nucleotide polymorphisms (SNPs) of CYP2E1-rs2031920, CYP2E1-rs6413432, GSTP1-rs947894, MPO-rs2333227 and NQO1-rs1800566 were genotyped by PCR-based RFLP, sequencing and TaqMan assay in 358 NPC cases and 629 controls (phase I cohort). Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). To confirm our results, sixteen tag SNPs for GSTP1, MPO, NQO1 (which 100% covered these genes), and 4 functional SNPs of CYP2E1 were genotyped in another cohort of 213 NPC cases and 230 controls (phase II cohort). Results: No significant associations in NPC risk were observed for the five polymorphisms tested in the phase I cohort. In an additional stratified analysis for phase I, there was no significant association between cases and controls in NPC high risk population (EBV/IgA/VCA positive population). Analysis of 14 tagging SNPs within the same genes in an independent phase II cohort were in agreement with no SNPs significantly associated with NPC. Conclusions: Our results suggest that polymorphism of CYP2E1, GSTP1, MPO and NQO1 genes does not contribute to overall NPC risk in a Han Chinese in southern China. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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4. A population-based study to investigate host genetic factors associated with hepatitis B infection and pathogenesis in the Chinese population.
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Zheng Zeng, Li Guan, Ping An, Shan Sun, O'Brien, Stephen J., and Winkler, Cheryl A.
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CASE studies , *HEPATITIS B virus , *CHINESE people , *CIRRHOSIS of the liver , *LIVER cancer , *DISEASES - Abstract
Background: Hepatitis B virus (HBV) infection is a significant public health problem that may lead to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Approximately 30% of the world's population has been infected with HBV and approximately 350 million (5-6%) are persistent carriers. More than 120 million Chinese are infected with HBV. The role of host genetic factors and their interactions with environmental factors leading to chronic HBV infection and its complications are not well understood. We believe that a better understanding of these factors and interactions will lead to more effective diagnostic and therapeutic options. Methods/Design: This is a population-based, case-control study protocol to enroll 2200 Han Chinese from medical centers in northern and western China. Adult subjects in the following groups are being enrolled: healthy donors (n = 200), HBV infected persons achieving virus clearance (n = 400), asymptomatic HBV persistent carriers (n = 400), chronic hepatitis B cases (n = 400), decompensated liver cirrhosis with HBV infection cases (n = 400), and hepatocellular carcinoma with HBV infection cases (n = 400). In addition, for haplotype inference and quality control of sample handling and genotyping results, children of 1000 cases will be asked to provide a buccal sample for DNA extraction. With the exception of adult patients presenting with liver cirrhosis or HCC, all other cases and controls will be 40 years or older at enrollment. A questionnaire is being administered to capture dietary and environmental risk factors. Both candidate-gene and genome-wide association approaches will be used to assess the role of single genetic factors and higher order interactions with other genetic or environmental factors in HBV diseases. Conclusion: This study is designed and powered to detect single gene effects as well as gene-gene and environmental-gene interactions. The identification of allelic polymorphisms in genes involved in the pathway leading to chronic viral infection, liver cirrhosis and, ultimately, hepatocellular carcinoma would provide insights to those factors leading to HBV replication, liver inflammation, fibrosis, and the carcinogenic process. An understanding of the contribution of host genetic factors and their interactions may inform public health policy, improve diagnostics and clinical management, and provide targets for drug development. [ABSTRACT FROM AUTHOR]
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- 2008
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5. Patterns of Genetic Diversity in Remaining Giant Panda Populations.
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Lu, Zhi, Johnson, Warren E., Menotti‐Raymond, Marilyn, Yuhki, Naoya, Martenson, Janice S., Mainka, Susan, Shi‐Qiang, Huang, Zhihe, Zheng, Li, Guanghan, Pan, Wenshi, Mao, Xiarong, and O'Brien, Stephen J.
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PANDAS , *WILDLIFE conservation , *ENDANGERED species - Abstract
Abstract: The giant panda (Ailuropoda melanoleuca) is among the more familiar symbols of species conservation. The protection of giant panda populations has been aided recently by the establishment of more and better-managed reserves in existing panda habitat located in six mountain ranges in western China. These remaining populations are becoming increasingly isolated from one another, however, leading to the concern that historic patterns of gene flow will be disrupted and that reduced population sizes will lead to diminished genetic variability. We analyzed four categories of molecular genetic markers (mtDNA restriction-fragment-length polymorphisms [RFLP], mtDNA control region sequences, nuclear multilocus DNA fingerprints, and microsatellite size variation) in giant pandas from three mountain populations (Qionglai, Minshan, and Qinling) to assess current levels of genetic diversity and to detect evidence of historic population subdivisions. The three populations had moderate levels of genetic diversity compared with similarly studied carnivores for all four gene measures, with a slight but consistent reduction in variability apparent in the smaller Qinling population. That population also showed significant differentiation consistent with its isolation since historic times. From a strictly genetic perspective, the giant panda species and the three populations look promising insofar as they have retained a large amount of genetic diversity in each population, although evidence of recent population reduction—likely from habitat loss—is apparent. Ecological management to increase habitat, population expansion, and gene flow would seem an effective strategy to stabilize the decline of this endangered species. [ABSTRACT FROM AUTHOR]
- Published
- 2001
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6. Genome-Wide and Differential Proteomic Analysis of Hepatitis B Virus and Aflatoxin B1 Related Hepatocellular Carcinoma in Guangxi, China.
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Qi, Lu-Nan, Li, Le-Qun, Chen, Yuan-Yuan, Chen, Zhao-Hong, Bai, Tao, Xiang, Bang-De, Qin, Xiao, Xiao, Kai-Yin, Peng, Min-Hao, Liu, Zhi-Ming, Liu, Tang-Wei, Qin, Xue, Li, Shan, Han, Ze-Guang, Mo, Zeng-Nan, Santella, Regina M., Winkler, Cheryl A., O’Brien, Stephen J., and Peng, Tao
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PROTEOMICS , *HEPATITIS B virus , *AFLATOXINS , *LIVER diseases , *LIVER cancer patients , *GENE expression , *GENETICS - Abstract
Both hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure can cause liver damage as well as increase the probability of hepatocellular carcinoma (HCC). To investigate the underlying genetic changes that may influence development of HCC associated with HBV infection and AFB1 exposure, HCC patients were subdivided into 4 groups depending upon HBV and AFB1 exposure status: (HBV(+)/AFB1(+), HBV(+)/AFB1(-), HBV(-)/AFB1(+), HBV(-)/AFB1(-)). Genetic abnormalities and protein expression profiles were analyzed by array-based comparative genomic hybridization and isobaric tagging for quantitation. A total of 573 chromosomal aberrations (CNAs) including 184 increased and 389 decreased were detected in our study population. Twenty-five recurrently altered regions (RARs; chromosomal alterations observed in ≥10 patients) in chromosomes were identified. Loss of 4q13.3-q35.2, 13q12.1-q21.2 and gain of 7q11.2-q35 were observed with a higher frequency in the HBV(+)/AFB1(+), HBV(+)/AFB1(-) and HBV(-)/AFB1(+) groups compared to the HBV(-)/AFB(-) group. Loss of 8p12-p23.2 was associated with high TNM stage tumors (P = 0.038) and was an unfavorable prognostic factor for tumor-free survival (P =0.045). A total of 133 differentially expressed proteins were identified in iTRAQ proteomics analysis, 69 (51.8%) of which mapped within identified RARs. The most common biological processes affected by HBV and AFB1 status in HCC tumorigenesis were detoxification and drug metabolism pathways, antigen processing and anti-apoptosis pathways. Expression of AKR1B10 was increased significantly in the HBV(+)/AFB1(+) and HBV(-)/AFB1(+) groups. A significant correlation between the expression of AKR1B10 mRNA and protein levels as well as AKR1B10 copy number was observered, which suggest that AKR1B10 may play a role in AFB1-related hepatocarcinogenesis. In summary, a number of genetic and gene expression alterations were found to be associated with HBV and AFB1- related HCC. The possible synergistic effects of HBV and AFB1 in hepatocarcinogenesis warrant further investigations. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
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