PMID- 23592712
OWN - NLM
STAT- MEDLINE
DCOM- 20140530
LR  - 20140407
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Linking)
VI  - 73
IP  - 5
DP  - 2014 May
TI  - Genetics of toll like receptor 9 in ANCA associated vasculitides.
PG  - 890-6
LID - 10.1136/annrheumdis-2012-202803 [doi]
AB  - OBJECTIVES: To investigate the contribution of genetic polymorphisms of toll like 
      receptor (TLR) 9 and related genes on the susceptibility and clinical 
      manifestation of anti-neutrophil cytoplasmic antibody (ANCA) associated 
      vasculitides (AAV). METHODS: Four single nucleotide polymorphisms (SNPs) in TLR9 
      were genotyped in 863 German AAV cases and 1344 healthy controls. Significant 
      results were replicated in a cohort of 426 Dutch and British AAV cases. 11 
      polymorphisms in TLR9 related genes were studied concomitantly. RESULTS: A strong 
      association of TLR9 genotypes and haplotypes with granulomatosis with 
      polyangiitis was observed as well as a contrariwise association with microscopic 
      polyangiitis. The association was confirmed when cases were compared according to 
      ANCA status rather than to clinical entity. This was partly replicated in the 
      second cohort leading to a striking overall difference in TLR9 allele/haplotype 
      frequencies between proteinase 3 (PR3) ANCA+ and myeloperoxidase (MPO) ANCA+ 
      cases (p=0.00000398, pc=0.000016, OR 1.68 (95% CI 1.35 to 2.1) for rs352140; 
      p=0.000011, pc=0.000044, OR 1.64 (95% CI 1.31 to 2.04) for a 3-SNP haplotype). No 
      significant association or epistatic effect was detected for TLR9 related genes: 
      interleukin 6, interleukin 23 receptor, myeloid differentiation primary response 
      88, TNF receptor-associated factor 6, interleukin-1 receptor-associated kinase 4, 
      discs large homolog 5 and nucleotide-binding oligomerisation domain containing 2. 
      CONCLUSIONS: We provide further evidence that PR3-ANCA+ AAV differs genetically 
      from MPO-ANCA+ AAV. TLR9 signalling may be involved in disease pathology, 
      favouring models of infectious agents triggering AAV development.
FAU - Husmann, C A
AU  - Husmann CA
AD  - Department of Human Genetics, Ruhr University, , Bochum, Germany.
FAU - Holle, J U
AU  - Holle JU
FAU - Moosig, F
AU  - Moosig F
FAU - Mueller, S
AU  - Mueller S
FAU - Wilde, B
AU  - Wilde B
FAU - Cohen Tervaert, J W
AU  - Cohen Tervaert JW
FAU - Harper, L
AU  - Harper L
FAU - Assmann, G
AU  - Assmann G
FAU - Gross, W L
AU  - Gross WL
FAU - Epplen, J T
AU  - Epplen JT
FAU - Wieczorek, S
AU  - Wieczorek S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130416
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (TLR9 protein, human)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Adult
MH  - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/*genetics
MH  - Case-Control Studies
MH  - Female
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genotype
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Male
MH  - Polymorphism, Single Nucleotide
MH  - Toll-Like Receptor 9/*genetics
OTO - NOTNLM
OT  - Autoantibodies
OT  - Gene Polymorphism
OT  - Granulomatosis with polyangiitis
EDAT- 2013/04/18 06:00
MHDA- 2014/05/31 06:00
CRDT- 2013/04/18 06:00
PHST- 2013/04/18 06:00 [entrez]
PHST- 2013/04/18 06:00 [pubmed]
PHST- 2014/05/31 06:00 [medline]
AID - annrheumdis-2012-202803 [pii]
AID - 10.1136/annrheumdis-2012-202803 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2014 May;73(5):890-6. doi: 10.1136/annrheumdis-2012-202803. Epub 
      2013 Apr 16.