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  1. Article ; Online: Rectal microbiota diversity in Kenyan MSM is inversely associated with frequency of receptive anal sex, independent of HIV status.

    Gebrebrhan, Henok / Kambaran, Cheli / Sivro, Aida / Adhiambo, Wendy / Siele, Naomi / Becker, Michael G / Li, Jie / Choi, Sandra / Mwatelah, Ruth S / Reyes, N Vincent / Akolo, Maureen / Njogu, Peter / Cholette, François / Ho, John / Kim, John / Peterson, Shelley W / Martin, Irene / Sandstrom, Paul / Mehta, Supriya D /
    Lorway, Robert R / Ball, T Blake / Kimani, Joshua / Mclaren, Paul J / Ji, Hezhao / McKinnon, Lyle R

    AIDS (London, England)

    2021  Volume 35, Issue 7, Page(s) 1091–1101

    Abstract: Objective: Both HIV infection and identifying as MSM have been linked to altered rectal microbiota composition, but few studies have studied sexual behavioural associations with rectal microbiota within MSM. In addition, most rectal microbiota studies ... ...

    Abstract Objective: Both HIV infection and identifying as MSM have been linked to altered rectal microbiota composition, but few studies have studied sexual behavioural associations with rectal microbiota within MSM. In addition, most rectal microbiota studies in MSM have been limited geographically to Europe and North America, and replication of findings in lower and middle-income countries is lacking.
    Design: A cross-sectional study.
    Methods: We enrolled MSM from Nairobi, Kenya, and determined their HIV/sexually transmitted infection status. Rectal specimens were obtained for 16s rRNA sequencing of the rectal microbiota, and sexual behaviour was characterized using a standardized questionnaire. Microbiome differences were modelled using nonparametric statistics, Bray-Curtis ecological distance metrics and analyses of differential taxa abundance. Multivariable linear regression was used to model HIV status and recent sexual activity as predictors of alpha diversity, controlling for a range of covariates.
    Results: Alpha diversity was consistently lower in Kenyan HIV-infected MSM (n = 80), including those on antiretroviral therapy (ART) compared with HIV-uninfected MSM. A statistical trend was observed for clustering of HIV status by Prevotella or Bacteroides dominance (P = 0.13). Several taxa were enriched in HIV-positive men, including Roseburia, Lachnospira, Streptococcus and Granulicatella. Receptive anal sex with several types of sexual partners (paying, regular, casual) was associated with lower Chao1 and Simpson diversity, independent of HIV status, while HIV infection was associated lower Chao1 (P = 0.030) but not Simpson diversity (P = 0.49).
    Conclusion: Both HIV infection and sexual behaviour were associated with rectal microflora alpha diversity, in particular richness, but not Prevotella spp. dominance, in Kenyan MSM. Associations were more robust for sexual behaviour.
    MeSH term(s) Cross-Sectional Studies ; Europe ; HIV Infections/complications ; Homosexuality, Male ; Humans ; Kenya ; Male ; Microbiota ; North America ; Prevalence ; RNA, Ribosomal, 16S/genetics ; Sexual Behavior ; Sexual and Gender Minorities
    Chemical Substances RNA, Ribosomal, 16S
    Language English
    Publishing date 2021-09-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639076-6
    ISSN 1473-5571 ; 0269-9370 ; 1350-2840
    ISSN (online) 1473-5571
    ISSN 0269-9370 ; 1350-2840
    DOI 10.1097/QAD.0000000000002829
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Host genetic predictors of the kynurenine pathway of tryptophan catabolism among treated HIV-infected Ugandans.

    Lee, Sulggi A / Mefford, Joel A / Huang, Yong / Witte, John S / Martin, Jeffrey N / Haas, David W / Mclaren, Paul J / Mushiroda, Taisei / Kubo, Michiaki / Byakwaga, Helen / Hunt, Peter W / Kroetz, Deanna L

    AIDS (London, England)

    2016  Volume 30, Issue 11, Page(s) 1807–1815

    Abstract: Objective: Plasma kynurenine/tryptophan ratio, a biomarker of indoleamine 2,3-dioxygenase-1 (IDO) activity, is a strong independent predictor of mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART) and may play a key role in HIV ... ...

    Abstract Objective: Plasma kynurenine/tryptophan ratio, a biomarker of indoleamine 2,3-dioxygenase-1 (IDO) activity, is a strong independent predictor of mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART) and may play a key role in HIV pathogenesis. We performed a genome-wide study to identify potential host genetic determinants of kynurenine/tryptophan ratio in HIV-infected ART-suppressed Ugandans.
    Design/methods: We performed genome-wide and exome array genotyping and measured plasma kynurenine/tryptophan ratio during the initial 6-12 months of suppressive ART in Ugandans. We evaluated more than 16 million single nucleotide polymorphisms in association with log10 kynurenine/tryptophan ratio using linear mixed models adjusted for cohort, sex, pregnancy, and ancestry.
    Results: Among 597 Ugandans, 62% were woman, median age was 35, median baseline CD4 cell count was 135 cells/μl, and median baseline HIV-1 RNA was 5.1 log10 copies/ml. Several polymorphisms in candidate genes TNF, IFNGR1, and TLR4 were associated with log10 kynurenine/tryptophan ratio (P < 5.0 × 10). An intergenic polymorphism between CSPG5 and ELP6 was genome-wide significant, whereas several others exhibited suggestive associations (P < 5.0 × 10), including genes encoding protein tyrosine phosphatases (PTPRM and PTPRN2) and the vitamin D metabolism gene, CYP24A1. Several of these single nucleotide polymorphisms were associated with markers of inflammation, coagulation, and monocyte activation, but did not replicate in a small US cohort (N = 262; 33% African-American).
    Conclusion: Our findings highlight a potentially important role of IFN-γ, TNF-α, and Toll-like receptor signaling in determining IDO activity and subsequent mortality risk in HIV-infected ART-suppressed Ugandans. These results also identify potential novel pathways involved in IDO immunoregulation. Further studies are needed to confirm these findings in treated HIV-infected populations.
    MeSH term(s) Adult ; Anti-Retroviral Agents/therapeutic use ; Female ; HIV Infections/drug therapy ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Interferon-gamma/metabolism ; Kynurenine/blood ; Kynurenine/metabolism ; Male ; Metabolism ; Plasma/chemistry ; Risk Assessment ; Signal Transduction ; Survival Analysis ; Toll-Like Receptors/metabolism ; Tryptophan/blood ; Tryptophan/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Uganda
    Chemical Substances Anti-Retroviral Agents ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Toll-Like Receptors ; Tumor Necrosis Factor-alpha ; Kynurenine (343-65-7) ; Interferon-gamma (82115-62-6) ; Tryptophan (8DUH1N11BX)
    Language English
    Publishing date 2016-01-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 639076-6
    ISSN 1473-5571 ; 0269-9370 ; 1350-2840
    ISSN (online) 1473-5571
    ISSN 0269-9370 ; 1350-2840
    DOI 10.1097/QAD.0000000000001124
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Microarray analysis of HIV resistant female sex workers reveal a gene expression signature pattern reminiscent of a lowered immune activation state.

    Songok, Elijah M / Luo, Ma / Liang, Ben / Mclaren, Paul / Kaefer, Nadine / Apidi, Winnie / Boucher, Genevieve / Kimani, Joshua / Wachihi, Charles / Sekaly, Rafick / Fowke, Keith / Ball, Blake T / Plummer, Francis A

    PloS one

    2012  Volume 7, Issue 1, Page(s) e30048

    Abstract: To identify novel biomarkers for HIV-1 resistance, including pathways that may be critical in anti-HIV-1 vaccine design, we carried out a gene expression analysis on blood samples obtained from HIV-1 highly exposed seronegatives (HESN) from a commercial ... ...

    Abstract To identify novel biomarkers for HIV-1 resistance, including pathways that may be critical in anti-HIV-1 vaccine design, we carried out a gene expression analysis on blood samples obtained from HIV-1 highly exposed seronegatives (HESN) from a commercial sex worker cohort in Nairobi and compared their profiles to HIV-1 negative controls. Whole blood samples were collected from 43 HIV-1 resistant sex workers and a similar number of controls. Total RNA was extracted and hybridized to the Affymetrix HUG 133 Plus 2.0 micro arrays (Affymetrix, Santa Clara CA). Output data was analysed through ArrayAssist software (Agilent, San Jose CA). More than 2,274 probe sets were differentially expressed in the HESN as compared to the control group (fold change ≥1.3; p value ≤0.0001, FDR <0.05). Unsupervised hierarchical clustering of the differentially expressed genes readily distinguished HESNs from controls. Pathway analysis through the KEGG signaling database revealed a majority of the impacted pathways (13 of 15, 87%) had genes that were significantly down regulated. The most down expressed pathways were glycolysis/gluconeogenesis, pentose phosphate, phosphatidyl inositol, natural killer cell cytotoxicity and T-cell receptor signaling. Ribosomal protein synthesis and tight junction genes were up regulated. We infer that the hallmark of HIV-1 resistance is down regulation of genes in key signaling pathways that HIV-1 depends on for infection.
    MeSH term(s) Cluster Analysis ; Cohort Studies ; Down-Regulation/genetics ; Down-Regulation/immunology ; Female ; Gene Expression Profiling ; HIV Infections/genetics ; HIV Infections/immunology ; HIV-1/immunology ; Humans ; Immunity, Innate/genetics ; Kenya ; Lymphocyte Activation/genetics ; Lymphocyte Activation/immunology ; Microarray Analysis ; Reverse Transcriptase Polymerase Chain Reaction ; Sex Workers ; Validation Studies as Topic
    Language English
    Publishing date 2012-01-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0030048
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis.

    Carmona, F David / Vaglio, Augusto / Mackie, Sarah L / Hernández-Rodríguez, José / Monach, Paul A / Castañeda, Santos / Solans, Roser / Morado, Inmaculada C / Narváez, Javier / Ramentol-Sintas, Marc / Pease, Colin T / Dasgupta, Bhaskar / Watts, Richard / Khalidi, Nader / Langford, Carol A / Ytterberg, Steven / Boiardi, Luigi / Beretta, Lorenzo / Govoni, Marcello /
    Emmi, Giacomo / Bonatti, Francesco / Cimmino, Marco A / Witte, Torsten / Neumann, Thomas / Holle, Julia / Schönau, Verena / Sailler, Laurent / Papo, Thomas / Haroche, Julien / Mahr, Alfred / Mouthon, Luc / Molberg, Øyvind / Diamantopoulos, Andreas P / Voskuyl, Alexandre / Brouwer, Elisabeth / Daikeler, Thomas / Berger, Christoph T / Molloy, Eamonn S / O'Neill, Lorraine / Blockmans, Daniel / Lie, Benedicte A / Mclaren, Paul / Vyse, Timothy J / Wijmenga, Cisca / Allanore, Yannick / Koeleman, Bobby P C / Barrett, Jennifer H / Cid, María C / Salvarani, Carlo / Merkel, Peter A / Morgan, Ann W / González-Gay, Miguel A / Martín, Javier

    American journal of human genetics

    2016  Volume 100, Issue 1, Page(s) 64–74

    Abstract: Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a ... ...

    Abstract Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10
    MeSH term(s) Aged ; Aged, 80 and over ; Alleles ; Cohort Studies ; Europe/ethnology ; Female ; Genetic Predisposition to Disease/genetics ; Genetic Variation ; Genome-Wide Association Study ; Giant Cell Arteritis/genetics ; Humans ; Male ; Neovascularization, Physiologic ; Plasminogen/genetics ; Polymorphism, Single Nucleotide/genetics ; Prolyl Hydroxylases/genetics ; Risk
    Chemical Substances Plasminogen (9001-91-6) ; P4HA2 protein, human (EC 1.14.11.-) ; Prolyl Hydroxylases (EC 1.14.11.-)
    Language English
    Publishing date 2016-12-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 219384-x
    ISSN 1537-6605 ; 0002-9297
    ISSN (online) 1537-6605
    ISSN 0002-9297
    DOI 10.1016/j.ajhg.2016.11.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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