ArticleJournal of acquired immune deficiency syndromes (1999)2019
Increasing Levels of Serum Heat Shock Protein 70 Precede the Development of AIDS-Defining Non-Hodgkin Lymphoma Among Carriers of HLA-B8-DR3.
Brahim Aissani, Otoniel Martinez-Maza, Richard A Kaslow, Howard W Wiener, Jay H Bream, Valentina Stosor, Jeremy J Martinson, Lisa P Jacobson, Sadeep Shrestha
Open access · hybridAbstract readMulticenter Study
Article in Journal of acquired immune deficiency syndromes (1999), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed, 2 citations in OpenAlex.
Richard A KaslowDepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, AL.
Howard W WienerDepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, AL.
Jay H BreamDepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Valentina StosorDepartment of Medicine, Northwestern University, Chicago, IL.
Jeremy J MartinsonDepartment of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA.
Lisa P JacobsonDepartment of Epidemiology, Johns Hopkins University, Baltimore, MD.
Sadeep ShresthaDepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, AL.
University of Alabama at Birmingham · USJohns Hopkins University · USBeijing Obstetrics and Gynecology Hospital · CNNorthwestern University · USUniversity of Pittsburgh · US
Funding
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6M
NATURAL HISTORY OF AIDS IN HOMOSEXUAL MENU01AI035040 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DETELS, ROGER, MARTINEZ-MAZA, OTONIEL · 1993 to 2018
$75.2M
University of Pittsburgh Multicenter AIDS Cohort Study (MACS)U01AI035041 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MARTINSON, JEREMY JAMES, RINALDO, CHARLES R · 1993 to 2018
$71.4M
MULTICENTER AIDS COHORT STUDYU01AI035039 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WOLINSKY, STEVEN M · 1993 to 2018
$66.4M
Multicenter Aids Cohort Study- Part B (Baltimore Site)U01AI035042 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BROWN, TODD T, MARGOLICK, JOSEPH B. · 1993 to 2018
$61.5M
Clinical Research Sites for the MACS/WIHS Combined Cohort Study (MACS/WIHS-CCS) - Baltimore/Wash DC Center - Admin Supplement: Vision and dual sensory loss in HIV-infected older adultsU01HL146201 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI TODD T BROWN, Joseph B. Margolick · 2019 to 2026
$33.7M
METHODOLOGICAL EXPERTISE IN INTREPRETING MACS DATAU01AI035043 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JACOBSON, LISA P · 1993 to 2011
$26.9M
Center for the Analysis & Management of the Multicenter AIDS Cohort StudyUM1AI035043 · NIAID · JOHNS HOPKINS UNIVERSITY · PI D'SOUZA, GYPSYAMBER, JACOBSON, LISA P · 2012 to 2018
$20.7M
Institute for Clinical and Translational ResearchUL1TR000424 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2012 to 2012
$6.0M
MULTICENTER AIDS COHORT STUDY PATHOGENESIS RESEARCH LABSU01AI037613 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JAMIESON-KARAVODIN, BETH DEIRDRE · 1995 to 2003
$3.4M
MULTICENTER AIDS COHORT STUDY PATHOGENESIS RESEARCHU01AI037984 · NIAID · JOHNS HOPKINS UNIVERSITY · PI MARGOLICK, JOSEPH B. · 1995 to 2003
$3.1M
ZIDOVUDINE WITH PROBENECID--EFFECTS OF PROBENECID ON ZIDOVUDINEM01RR000722 · NCRR · JOHNS HOPKINS UNIVERSITY · 1985 to 1996
backgroundWe hypothesized that carriage of presumably high Hsp70-producing gene variants on a specific human major histocompatibility complex haplotype, the 8.1 ancestral haplotype (8.1AH), may predispose HIV-infected individuals to AIDS-non-Hodgkin lymphoma (NHL).
settingWe compared serum Hsp70 levels in the years preceding the diagnosis of AIDS-NHL in a matched case-control study (n = 151 pairs) nested in the Multicenter AIDS Cohort Study.
methodsWe tested the impact of 8.1AH-specific single-nucleotide polymorphism (SNP) and joint SNP-human leukocyte antigen extended haplotypes previously associated with AIDS-NHL in the Multicenter AIDS Cohort Study on the circulating Hsp70 levels in mixed linear models.
resultsWe report elevated serum levels of Hsp70 in the 4 years preceding the diagnosis of AIDS-NHL in cases that carry 8.1AH, but not in noncarrier cases and not in carrier- or non-carrier-matched controls. The strongest predictor of higher serum Hsp70 was the haplotype A-G-A-C formed by SNPs rs537160(A) and rs1270942(G) in the complement factor CFB gene cluster, and rs2072633(A) and rs6467(C) in nearby RDBP and CYP21A2 located 70 Kb apart from the Hsp70 gene cluster. The association with A-G-A-C haplotype (beta = 0.718; standard error = 0.182; P = 0.0002) and with other 8.1AH-specific haplotypes including the high-producing tumor necrosis factor-alpha haplotype rs909253(G)-rs1800629(A) (beta = 0.308; standard error = 0.140; P = 0.032) were observed only with NHL identified as an AIDS-defining condition, but not as a post-AIDS condition, nor in combined AIDS and post-AIDS cases.
conclusionOur combined genetic and functional approach suggests that the altered level of Hsp70 is a correlate of 8.1AH-mediated AIDS-NHL. Further investigation of the Hsp70 gene cluster and nearby loci that are tagged by A-G-A-C could better elucidate the genetic determinants of the malignancy.
Indexed as
Case-Control StudiesGenetic Predisposition to DiseaseHaplotypesHIV InfectionsHLA-B8 AntigenHLA-DR3 AntigenHomosexuality, MaleHSP70 Heat-Shock ProteinsHumansLymphoma, AIDS-RelatedLymphoma, Non-HodgkinMaleMultigene FamilyPolymorphism, Single NucleotideHLA-B8 AntigenHLA-DR3 AntigenHSP70 Heat-Shock Proteins
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Increasing Levels of Serum Heat Shock Protein 70 Precede the Development of AIDS-Defining Non-Hodgkin Lymphoma Among Carriers of HLA-B8-DR3. · full record | OpenQuestion