13 results on '"O'BRIEN, STEPHEN J."'
Search Results
2. THE INFLUENCE OF HLA GENOTYPE ON AIDS.
- Author
-
Carrington, Mary and O'Brien, Stephen J.
- Subjects
- *
HIV infections , *AIDS , *GENETIC epidemiology , *HLA class II antigens - Abstract
Genetic resistance to infectious diseases is likely to involve a complex array of immune-response and other genes with variants that impose subtle but significant consequences on gene expression or protein function. We have gained considerable insight into the genetic determinants of HIV-1 disease, and the HLA class I genes appear to be highly influential in this regard. Numerous reports have identified a role for HLA genotype in AIDS outcomes, implicating many HLA alleles in various aspects of HIV disease. Here we review the HLA associations with progression to AIDS that have been consistently affirmed and discuss the underlying mechanisms behind some of these associations based on functional studies of immune cell recognition. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
3. Genome-wide association study reveals genetic variants associated with HIV-1C infection in a Botswana study population.
- Author
-
Shevchenko, Andrey K., Zhernakova, Daria V., Malov, Sergey V., Komissarov, Alexey, Kolchanova, Sofia M., Tamazian, Gaik, Antonik, Alexey, Cherkasov, Nikolay, Kliver, Sergey, Turenko, Anastasiia, Rotkevich, Mikhail, Evsyukov, Igor, Vlahov, David, Thami, Prisca K., Gaseitsiwe, Simani, Novitsky, Vladimir, Essex, Myron, and O'Brien, Stephen J.
- Subjects
- *
GENOME-wide association studies , *GENETIC variation , *HIV infections , *HIV , *AIDS - Abstract
Although there have been many studies of gene variant association with different stages of HIV/AIDS progression in United States and European cohorts, few gene-association studies have assessed genic determinants in sub-Saharan African populations, which have the highest density of HIV infections worldwide. We carried out genome-wide association studies on 766 study participants at risk for HIV-1 subtype C (HIV-1C) infection in Botswana. Three gene associations (AP3B1, PTPRA, and NEO1) were shown to have significant association with HIV-1C acquisition. Each gene association was replicated within Botswana or in the United States-African American or United States-European American AIDS cohorts or in both. Each associated gene has a prior reported influence on HIV/AIDS pathogenesis. Thirteen previously discovered AIDS restriction genes were further replicated in the Botswana cohorts, extending our confidence in these prior AIDS restriction gene reports. This work presents an early step toward the identification of genetic variants associated with and affecting HIV acquisition or AIDS progression in the understudied HIV-1C afflicted Botswana population. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
4. Genetic Variants in Nuclear-Encoded Mitochondrial Genes Influence AIDS Progression.
- Author
-
Hendrickson, Sher L., Lautenberger, James A., Chinn, Leslie Wei, Malasky, Michael, Sezgin, Efe, Kingsley, Lawrence A., Goedert, James J., Kirk, Gregory D., Gomperts, Edward D., Buchbinder, Susan P., Troyer, Jennifer L., and O'Brien, Stephen J.
- Subjects
- *
AIDS , *HIV infections , *GENES , *GENETICS , *MITOCHONDRIA , *MORPHOLOGY , *MITOCHONDRIAL DNA , *NUCLEOTIDES , *GENETIC polymorphisms - Abstract
Background: The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression. Methodology/Principal Findings: Here we explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs) influence AIDS progression among HIV-1 infected patients. We examined NEMPs for association with the rate of AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping array of 1,455 European American patients from five US AIDS cohorts. Successfully genotyped SNPs gave 50% or better haplotype coverage for 679 of known NEMP genes. With a Bonferroni adjustment for the number of genes and tests examined, multiple SNPs within two NEMP genes showed significant association with AIDS progression: acyl-CoA synthetase medium-chain family member 4 (ACSM4) on chromosome 12 and peroxisomal D3,D2-enoyl- CoA isomerase (PECI) on chromosome 6. Conclusions: Our previous studies on mitochondrial DNA showed that European haplogroups with presumed functional differences were associated with AIDS progression and HAART mediated adverse events. The modest influences of nuclear-encoded mitochondrial genes found in the current study add support to the idea that mitochondrial function plays a role in AIDS pathogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
5. Association of Y chromosome haplogroup I with HIV progression, and HAART outcome.
- Author
-
Sezgin, Efe, Lind, Joanne M., Shrestha, Sadeep, Hendrickson, Sher, Goedert, James J., Donfield, Sharyne, Kirk, Gregory D., Phair, John P., Troyer, Jennifer L., O'Brien, Stephen J., and Smith, Michael W.
- Subjects
- *
HIV infections , *THERAPEUTICS , *EUROPEAN Americans , *AFRICAN Americans , *AIDS , *Y chromosome , *SEX chromosomes - Abstract
The host genetic basis of differential outcomes in HIV infection, progression, viral load set point and highly active retroviral therapy (HAART) responses was examined for the common Y haplogroups in European Americans and African Americans. Accelerated progression to acquired immune deficiency syndrome (AIDS) and related death in European Americans among Y chromosome haplogroup I (Y-I) subjects was discovered. Additionally, Y-I haplogroup subjects on HAART took a longer time to HIV-1 viral suppression and were more likely to fail HAART. Both the accelerated progression and longer time to viral suppression results observed in haplogroup Y-I were significant after false-discovery-rate corrections. A higher frequency of AIDS-defining illnesses was also observed in haplogroup Y-I. These effects were independent of the previously identified autosomal AIDS restriction genes. When the Y-I haplogroup subjects were further subdivided into six I subhaplogroups, no one subhaplogroup accounted for the effects on HIV progression, viral load or HAART response. Adjustment of the analyses for population stratification found significant and concordant haplogroup Y-I results. The Y chromosome haplogroup analyses of HIV infection and progression in African Americans were not significant. Our results suggest that one or more loci on the Y chromosome found on haplogroup Y-I have an effect on AIDS progression and treatment responses in European Americans. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
6. Host Genetic Influences on Highly Active Antiretroviral Therapy Efficacy and AIDS-Free Survival.
- Author
-
Hendrickson, Sher L., Jacobson, Lisa P., Nelson, George W., Phair, John P., Lautenberger, James, Johnson, Randall C., Kingsley, Lawrence, Margolick, Joseph B., Detels, Roger, Goedert, James J., and O'Brien, Stephen J.
- Subjects
- *
AIDS , *HIV infections , *HIV , *ANTIVIRAL agents , *THERAPEUTICS - Abstract
The article studies the influence of AIDS restriction genes and haplotypes of the CCR5 P1 promoter and RANTES variants among HIV-1 infected patients on highly active antiretroviral therapy in the Multicenter AIDS Cohort Study and the Multicenter Hemophilia Cohort Study. It examines a range of genes that were predicted to influence HAART through various interactions with the HIV life cycle and drug metabolism.
- Published
- 2008
- Full Text
- View/download PDF
7. Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1.
- Author
-
Martin, Maureen P, Qi, Ying, Gao, Xiaojiang, Yamada, Eriko, Martin, Jeffrey N, Pereyra, Florencia, Colombo, Sara, Brown, Elizabeth E, Shupert, W Lesley, Phair, John, Goedert, James J, Buchbinder, Susan, Kirk, Gregory D, Telenti, Amalio, Connors, Mark, O'Brien, Stephen J, Walker, Bruce D, Parham, Peter, Deeks, Steven G, and McVicar, Daniel W
- Subjects
- *
HIV , *HTLV , *HIV infections , *KILLER cells , *AIDS - Abstract
Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)+ individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
8. Dominant Effects of CCR2-CCRS Haplotypes in HIV-1 Disease Progression.
- Author
-
Winkler, Cheryl A., Hendel, Houria, Carrington, Mary, Smith, Michael W., Nelson, George W., O'Brien, Stephen J., Phair, John, Vlahov, David, Jacobson, Lisa P., Rappaport, Jay, Vasilescu, Alexandre, Bertin-Maghit, Sebastien, Ping An, Wei Lu, Andrieu, Jean-Marie, Schächter, Fran çois, Therwath, Amu, and Zagury, Jean-François
- Subjects
- *
CHEMOKINES , *INFLAMMATORY mediators , *AIDS , *HIV infections , *PROMOTERS (Genetics) , *GENETIC transcription - Abstract
Reports the relative contributions to AIDS progression of three promoter haplotypes of CCR2-CCR5. Comparison of the rapid progression with a seroconverter control group including intermediate progressors to AIDS; Data indicating that factors other than CCR5 or CCR2 genetic variants must be responsible for the long-term maintenance of nonprogression.
- Published
- 2004
- Full Text
- View/download PDF
9. Lack of Associations Between HLA Class II Alleles and Resistance to HIV-1 Infection Among White, Non-Hispanic Homosexual Men.
- Author
-
Liu, Chenglong, Carrington, Mary, Kaslow, Richard A., Gao, Xiaojiang, Rinaldo, Charles R., Jacobson, Lisa P., Margolick, Joseph B., Phair, John, O'Brien, Stephen J., and Detels, Roger
- Subjects
- *
HLA class II antigens , *NATURAL immunity , *HIV infections , *GAY men , *WHITE men , *WHITE people , *AIDS - Abstract
Discusses the lack of associations between HLA class II alleles and resistance to HIV-1 infection among white, non-Hispanic, gay men. HLA class II alleles were molecularly typed for 100 high-risk seronegative men; Transporter associated with antigen presentation 2; Linkage disequilibrium with some HLA class II alleles.
- Published
- 2004
- Full Text
- View/download PDF
10. Haplotype diversity in the interleukin-4 gene is not associated with HIV-1 transmission and AIDS progression.
- Author
-
Modi, William S., O'Brien, Thomas R., Vlahov, David, Buchbinder, Susan, Gomperts, Edward, Phair, John, O'Brien, Stephen J., and Winkler, Cheryl
- Subjects
- *
INTERLEUKIN-4 , *HIV infection transmission , *HIV infections , *GENETIC recombination , *CYTOKINES , *IMMUNOGENETICS - Abstract
Interleukin-4 (IL-4) is a pleiotropic cytokine produced primarily by activated CD4+ T lymphocytes, mast cells, and basophils. It modulates the functions of a variety of cell types involved with the immune response. This cytokine differentially regulates two major HIV-1 coreceptors and activates viral expression, and is thus a reasonable candidate gene for analyses in HIV-1/AIDS cohort studies. Population genetic variation in five single nucleotide polymorphisms (SNPs) in the 5′ region of the IL-4 gene was assessed in five racial groups. Neutrality tests reveal that the populations are evolving in accord with the infinite-sites model. However, coalescent simulations suggest greater haplotype diversity among African Americans than expected. This increased variation is presumably attributable to recombination or gene conversion. Genetic epidemiological analyses were conducted among European American and African American participants enrolled in five USA-based HIV-1/AIDS cohorts. One SNP, -589T, known to influence IL-4 transcription was previously shown to be associated with HIV-1/AIDS in both Japanese and French populations. Present analyses failed to identify any significant associations with HIV-1 infection or progression to AIDS. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
11. Effect of Host Genetics on Incidence of HIV Neuroretinal Disorder in Patients With AIDS.
- Author
-
Sezgin, Efe, Hendrickson, Sher L., Jabs, Douglas A., Van Natta, Mark L., Lewis, Richard A., Troyer, Jennifer L., and O'Brien, Stephen J.
- Subjects
- *
HIV-positive persons , *AIDS , *CONTRAST sensitivity (Vision) , *GENES , *ANTIVIRAL agents , *HIV infections , *RETINAL degeneration , *HIV , *PATIENTS - Abstract
The article presents a study on the effect of host genetics on human immunodeficiency virus neuroretinal disorder (HIV-NRD) in patients with AIDS. It notes the loss of contrast sensitivity that is sufficient to impair reading speed. It mentions the validated AIDS restriction gene variants in evaluating the effect of host genes on HIV-NRD which has been implicated to influence HIV-1 infection, AIDS progression, therapy response, and antiviral drug metabolism.
- Published
- 2010
- Full Text
- View/download PDF
12. AIDS restriction HLA allotypes target distinct intervals of HIV-1 pathogenesis.
- Author
-
Xiaojiang Gao, Bashirova, Arman, Iversen, Astrid K. N., Phair, John, Goedert, James J., Buchbinder, Susan, Hoots, Keith, Vlahov, David, Altfeld, Marcus, O'Brien, Stephen J., and Carrington, Mary
- Subjects
- *
AIDS , *HLA histocompatibility antigens , *HISTOCOMPATIBILITY antigens , *HIV infections , *LENTIVIRUS diseases - Abstract
An effective acquired immune response to infectious agents mediated by HLA-restricted T-cell recognition can target different stages of disease pathogenesis. We show here that three distinct HLA alleles known to alter the overall rate of AIDS progression act during distinct intervals after HIV-1 infection. The discrete timing of HLA allele influence suggests alternative functional mechanisms in immune defense against this dynamic and chronic immunosuppressive disease. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
13. Association of Host Genetic Risk Factors With the Course of Cytomegalovirus Retinitis in Patients Infected With Human Immunodeficiency Virus
- Author
-
Sezgin, Efe, van Natta, Mark L., Ahuja, Alka, Lyon, Alice, Srivastava, Sunil, Troyer, Jennifer L., O'Brien, Stephen J., and Jabs, Douglas A.
- Subjects
- *
CYTOMEGALOVIRUS retinitis , *HIGHLY active antiretroviral therapy , *TREATMENT effectiveness , *HIV infections , *DISEASE progression , *AIDS , *ANTIRETROVIRAL agents , *RETINAL detachment , *GENETICS - Abstract
Purpose: To evaluate the effects of previously reported host genetics factors that influence cytomegalovirus (CMV) retinitis incidence, progression to acquired immune deficiency syndrome (AIDS), and efficacy of highly active antiretroviral therapy (HAART) for mortality, retinitis progression, and retinal detachment in patients with CMV retinitis and AIDS in the era of HAART. Design: Prospective, multicenter, observational study. Methods: Cox proportional hazards model based genetic association tests examined the influence of IL-10R1_S420L, CCR5-Δ32, CCR2-V64I, CCR5 promoter, and SDF-3′A polymorphisms among patients with mortality, retinitis progression, and retinal detachment. Participants were 203 European-American and 117 African-American patients with AIDS and CMV retinitis. Results: European-American patients with the CCR5 +.P1.+ promoter haplotype showed increased risk for mortality (hazard ratio [HR] = 1.83; 95% confidence interval [CI]: 1.00-3.40; P = .05). Although the same haplotype also trended for increased risk for mortality in African-American patients, the result was not significant (HR = 2.28; 95% CI: 0.93-5.60; P = .07). However, this haplotype was associated with faster retinitis progression in African Americans (HR = 5.22; 95% CI: 1.54-17.71; P = .007). Increased risk of retinitis progression was also evident for African-American patients with the SDF1-3′A variant (HR = 3.89; 95% CI: 1.42-10.60; P = .008). In addition, the SDF1-3′A variant increased the retinal detachment risk in this patient group (HR = 3.05; 95% CI: 1.01-9.16; P = .05). Conclusion: Besides overall immune health, host genetic factors influence mortality, retinitis progression, and retinal detachment in patients with AIDS and CMV retinitis that are receiving HAART. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.