PMID- 28628665
OWN - NLM
STAT- MEDLINE
DCOM- 20170718
LR  - 20171107
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Linking)
VI  - 13
IP  - 6
DP  - 2017 Jun
TI  - A chromosome 5q31.1 locus associates with tuberculin skin test reactivity in
      HIV-positive individuals from tuberculosis hyper-endemic regions in east Africa.
PG  - e1006710
LID - 10.1371/journal.pgen.1006710 [doi]
AB  - One in three people has been infected with Mycobacterium tuberculosis (MTB), and 
      the risk for MTB infection in HIV-infected individuals is even higher. We
      hypothesized that HIV-positive individuals living in tuberculosis-endemic regions
      who do not get infected by Mycobacterium tuberculosis are genetically resistant. 
      Using an "experiment of nature" design that proved successful in our previous
      work, we performed a genome-wide association study of tuberculin skin test
      positivity using 469 HIV-positive patients from prospective study cohorts of
      tuberculosis from Tanzania and Uganda to identify genetic loci associated with
      MTB infection in the context of HIV-infection. Among these individuals, 244
      tested were tuberculin skin test (TST) positive either at enrollment or during
      the >8 year follow up, while 225 were not. We identified a genome-wide
      significant association between a dominant model of rs877356 and binary TST
      status in the combined cohort (Odds ratio = 0.2671, p = 1.22x10-8). Association
      was replicated with similar significance when examining TST induration as a
      continuous trait. The variant lies in the 5q31.1 region, 57kb downstream from
      IL9. Two-locus analyses of association of variants near rs877356 showed a
      haplotype comprised of rs877356 and an IL9 missense variant, rs2069885, had the
      most significant association (p = 1.59x10-12). We also replicated previously
      linked loci on chromosomes 2, 5, and 11. IL9 is a cytokine produced by mast cells
      and TH2 cells during inflammatory responses, providing a possible link between
      airway inflammation and protection from MTB infection. Our results indicate that 
      studying uninfected, HIV-positive participants with extensive exposure increases 
      the power to detect associations in complex infectious disease.
FAU - Sobota, Rafal S
AU  - Sobota RS
AUID- ORCID: http://orcid.org/0000-0002-5945-5830
AD  - Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee,
      United States of America.
AD  - Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of 
      America.
FAU - Stein, Catherine M
AU  - Stein CM
AD  - Department of Population and Quantitative Health Sciences, Case Western Reserve
      University, Cleveland, Ohio, United States of America.
AD  - Tuberculosis Research Unit, Case Western Reserve University, Cleveland, Ohio,
      United States of America.
FAU - Kodaman, Nuri
AU  - Kodaman N
AD  - Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee,
      United States of America.
AD  - Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of 
      America.
AD  - Department of Population and Quantitative Health Sciences, Case Western Reserve
      University, Cleveland, Ohio, United States of America.
FAU - Maro, Isaac
AU  - Maro I
AUID- ORCID: http://orcid.org/0000-0003-2136-9555
AD  - Tokyo Medical and Dental University, Tokyo, Japan.
FAU - Wieland-Alter, Wendy
AU  - Wieland-Alter W
AD  - Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of 
      America.
FAU - Igo, Robert P Jr
AU  - Igo RP Jr
AD  - Department of Population and Quantitative Health Sciences, Case Western Reserve
      University, Cleveland, Ohio, United States of America.
FAU - Magohe, Albert
AU  - Magohe A
AD  - Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
FAU - Malone, LaShaunda L
AU  - Malone LL
AD  - Tuberculosis Research Unit, Case Western Reserve University, Cleveland, Ohio,
      United States of America.
AD  - Uganda-CWRU Research Collaboration, Kampala, Uganda.
FAU - Chervenak, Keith
AU  - Chervenak K
AUID- ORCID: http://orcid.org/0000-0003-0834-7511
AD  - Tuberculosis Research Unit, Case Western Reserve University, Cleveland, Ohio,
      United States of America.
AD  - Uganda-CWRU Research Collaboration, Kampala, Uganda.
FAU - Hall, Noemi B
AU  - Hall NB
AD  - Department of Population and Quantitative Health Sciences, Case Western Reserve
      University, Cleveland, Ohio, United States of America.
FAU - Matee, Mecky
AU  - Matee M
AD  - Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
FAU - Mayanja-Kizza, Harriet
AU  - Mayanja-Kizza H
AD  - Uganda-CWRU Research Collaboration, Kampala, Uganda.
AD  - College of Health Sciences Makerere University and Mulago Hospital, Kampala,
      Uganda.
FAU - Joloba, Moses
AU  - Joloba M
AD  - Uganda-CWRU Research Collaboration, Kampala, Uganda.
AD  - College of Health Sciences Makerere University and Mulago Hospital, Kampala,
      Uganda.
FAU - Moore, Jason H
AU  - Moore JH
AD  - Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of 
      America.
AD  - Perelman School of Medicine at the University of Pennsylvania, Philadelphia,
      Pennsylvania, United States of America.
FAU - Scott, William K
AU  - Scott WK
AD  - John P. Hussman Institute for Human Genomics, University of Miami, Miami,
      Florida, United States of America.
FAU - Lahey, Timothy
AU  - Lahey T
AD  - Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of 
      America.
FAU - Boom, W Henry
AU  - Boom WH
AD  - Tuberculosis Research Unit, Case Western Reserve University, Cleveland, Ohio,
      United States of America.
FAU - von Reyn, C Fordham
AU  - von Reyn CF
AD  - Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of 
      America.
FAU - Williams, Scott M
AU  - Williams SM
AUID- ORCID: http://orcid.org/0000-0002-4835-9544
AD  - Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of 
      America.
AD  - Department of Population and Quantitative Health Sciences, Case Western Reserve
      University, Cleveland, Ohio, United States of America.
FAU - Sirugo, Giorgio
AU  - Sirugo G
AUID- ORCID: http://orcid.org/0000-0002-0244-6343
AD  - Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy.
LA  - eng
GR  - R01 AI116794/AI/NIAID NIH HHS/United States
GR  - T32 GM007347/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20170619
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
SB  - IM
MH  - Adult
MH  - Chromosomes, Human, Pair 5/*genetics
MH  - Endemic Diseases
MH  - Female
MH  - *Genome-Wide Association Study
MH  - HIV/genetics/pathogenicity
MH  - HIV Infections/complications/*genetics/microbiology/virology
MH  - Haplotypes/genetics
MH  - Humans
MH  - Male
MH  - Mycobacterium tuberculosis/genetics/pathogenicity
MH  - Skin Tests
MH  - Tanzania
MH  - Tuberculin Test
MH  - Tuberculosis/complications/*genetics/microbiology/virology
MH  - Uganda
PMC - PMC5495514
EDAT- 2017/06/20 06:00
MHDA- 2017/07/19 06:00
CRDT- 2017/06/20 06:00
PHST- 2016/10/13 00:00 [received]
PHST- 2017/03/22 00:00 [accepted]
PHST- 2017/07/03 00:00 [revised]
PHST- 2017/06/20 06:00 [pubmed]
PHST- 2017/07/19 06:00 [medline]
PHST- 2017/06/20 06:00 [entrez]
AID - 10.1371/journal.pgen.1006710 [doi]
AID - PGENETICS-D-16-02285 [pii]
PST - epublish
SO  - PLoS Genet. 2017 Jun 19;13(6):e1006710. doi: 10.1371/journal.pgen.1006710.
      eCollection 2017 Jun.