The CARD9 Polymorphisms rs4077515, rs10870077 and rs10781499 Are Uncoupled from Susceptibility to and Severity of Pulmonary Tuberculosis.
Genetic variants in the CARD9 gene predispose to inflammatory disorders and chronic infectious diseases. Tuberculosis (TB), a chronic infectious disease affecting the lung, is lethal in Card9-deficient mice. We hypothesized that polymorphisms in the CARD9 gene influence TB progression and disease-associated lung damage in humans. We tested genotype distributions of the CARD9 polymorphisms rs4077515, rs10781499 and rs10870077 in TB patients and healthy subjects in a Caucasian cohort. SNPs were in linkage disequilibrium and none of the haplotypes was significantly enriched in the TB group. We determined total and differential leukocyte count, erythrocyte sedimentation rate and plasma abundance of cytokines and chemokines as markers for systemic inflammation and scored chest X-rays to assess lung involvement in TB subjects. Most disease parameters segregated independently of the CARD9 haplotypes. In contrast to multifactorial chronic inflammation, selected genetic variants in the CARD9 gene leave host responses apparently unaffected in TB, at least in the population analyzed here.
University of Medicine and Pharmacy of Craiova, Human Genomics Laboratory, 200638 Craiova, Romania.
Ioana
I
Streata
Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
January
J
Weiner
University of Naples Federico II, Department of Agriculture, 80055 Naples, Italy.
Marco
M
Iannaconne
Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
Gayle
G
McEwen
"Tudor Vladimirescu" Pneumophtisiology Hospital Runcu, 217390 Gorj, Romania.
Marius Sorin
MS
Ciontea
"Tudor Vladimirescu" Pneumophtisiology Hospital Runcu, 217390 Gorj, Romania.
Marian
M
Olaru
University of Naples Federico II, Department of Agriculture, 80055 Naples, Italy.
Rosanna
R
Capparelli
University of Medicine and Pharmacy of Craiova, Human Genomics Laboratory, 200638 Craiova, Romania.
Mihai
M
Ioana
Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
Stefan H E
SH
Kaufmann
Max Planck Institute for Infection Biology, 10117 Berlin, Germany.
Anca
A
Dorhoi
Inflammation. 2015 Apr;38(2):691-6
25028104
Nat Genet. 2011 Mar;43(3):246-52
21297633
Annu Rev Immunol. 2001;19:93-129
11244032
PLoS One. 2014 Jan 21;9(1):e85915
24465786
Nature. 2006 Aug 10;442(7103):651-6
16862125
N Engl J Med. 2013 Feb 21;368(8):745-55
23425167
J Clin Immunol. 2015 Jul;35(5):486-90
26044242
Cell Host Microbe. 2015 Feb 11;17(2):252-9
25674984
N Engl J Med. 2009 Oct 29;361(18):1727-35
19864672
Front Microbiol. 2014 Sep 23;5:483
25295030
Nature. 2012 Nov 1;491(7422):119-24
23128233
Am J Hum Genet. 2008 May;82(5):1202-10
18439550
Nat Immunol. 2007 Feb;8(2):198-205
17187069
Nat Genet. 2011 Oct 09;43(11):1066-73
21983784
Nat Genet. 2010 Dec;42(12):1118-25
21102463
Genes Immun. 2010 Sep;11(6):490-6
20463747
Nat Genet. 2010 Apr;42(4):332-7
20228799
Am J Respir Crit Care Med. 2013 Nov 1;188(9):1137-46
24047412
Nat Immunol. 2010 Jan;11(1):63-9
19915568
Scand J Immunol. 2009 Mar;69(3):259-67
19281538
J Exp Med. 2010 Apr 12;207 (4):777-92
20351059
Hepatology. 2011 Jun;53(6):1977-85
21425313
Nat Immunol. 2014 Jun;15(6):538-45
24777530
Front Cell Infect Microbiol. 2016 Apr 05;6:39
27092298
J Allergy Clin Immunol. 2015 Jun;135(6):1558-68.e2
25702837
J Infect Dis. 2011 Oct 1;204(7):1138-45
21881131
Trends Immunol. 2013 Jun;34(6):243-50
23523010
J Immunol. 2013 Mar 1;190(5):1921-5
23355741
J Infect Dis. 2015 Apr 15;211(8):1241-50
25057046
PLoS Genet. 2013;9(9):e1003723
24068945