Genetic variation in toll-like receptor 9 and susceptibility to systemic lupus erythematosus.
OBJECTIVE
Autoantibodies produced by differentiated B cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE). The Toll-like receptor 9 (TLR-9) gene has recently emerged as an important costimulatory molecule for both B cells and dendritic cells that respond to chromatin immune complexes. Genetic variation affecting the function of TLR-9 may therefore increase or decrease the threshold of B cell or dendritic cell activation. This variability in activation threshold may, in turn, affect an individual's susceptibility to SLE. This study assessed the role of genetic variation within the TLR-9 gene in susceptibility to SLE.


METHODS
We genotyped 362 SLE-affected subject/parent trios for 10 single-nucleotide polymorphisms (SNPs) covering a 68,742-bp genomic segment that contains the TLR-9 gene and approximately 60 kb of flanking sequence. We analyzed the data using the transmission disequilibrium test.


RESULTS
There was no association of susceptibility to SLE with any of the 9 SNPs that generated usable data or the 8 haplotypes found at a frequency of >0.05 in this population. When analyzing the subset of 143 subjects with lupus nephritis, there was also no evidence of association between disease susceptibility and any SNP or haplotype.


CONCLUSIONS
These results indicate that there is no evidence that common (frequency higher than 5%) alleles of the TLR-9 gene contribute significantly to the genetic risk involved in susceptibility to SLE or lupus nephritis.
Department of Neurology, Harvard Medical School, Brigham & Women's Hospital, Boston, MA 02115, USA. pdejager@rics.bwh.harvard.edu
Philip L
PL
De Jager
Angela
A
Richardson
Tim J
TJ
Vyse
John D
JD
Rioux
D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*
C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9