INTRODUCTION: The Toll-like receptor 7 (TLR7) gene, encoded on human chromosome 
Xp22.3, is crucial for type I interferon production. A recent multicenter study 
in East Asian populations, comprising Chinese, Korean and Japanese participants, 
identified an association of a TLR7 single-nucleotide polymorphism (SNP) located 
in the 3' untranslated region (3' UTR), rs3853839, with systemic lupus 
erythematosus (SLE), especially in males, although some difference was observed 
among the tested populations. To test whether additional polymorphisms 
contribute to SLE in Japanese, we systematically analyzed the association of 
TLR7 with SLE in a Japanese female population.
METHODS: A case-control association study was conducted on eight tag SNPs in the 
TLR7 region, including rs3853839, in 344 Japanese females with SLE and 274 
healthy female controls.
RESULTS: In addition to rs3853839, two SNPs in intron 2, rs179019 and rs179010, 
which were in moderate linkage disequilibrium with each other (r2 = 0.53), 
showed an association with SLE (rs179019: P = 0.016, odds ratio (OR) 2.02, 95% 
confidence interval (95% CI) 1.15 to 3.54; rs179010: P = 0.018, OR 1.75, 95% CI 
1.10 to 2.80 (both under the recessive model)). Conditional logistic regression 
analysis revealed that the association of the intronic SNPs and the 3' UTR SNP 
remained significant after we adjusted them for each other. When only the 
patients and controls carrying the risk genotypes at the 3' UTR SNP position 
were analyzed, the risk of SLE was significantly increased when the individuals 
also carried the risk genotypes at both of the intronic SNPs (P = 0.0043, OR 
2.45, 95% CI 1.31 to 4.60). Furthermore, the haplotype containing the intronic 
risk alleles in addition to the 3' UTR risk allele was associated with SLE under 
the recessive model (P = 0.016, OR 2.37, 95% CI 1.17 to 4.80), but other 
haplotypes were not associated with SLE.
CONCLUSIONS: The TLR7 intronic SNPs rs179019 and rs179010 are associated with 
SLE independently of the 3' UTR SNP rs3853839 in Japanese women. Our findings 
support a role of TLR7 in predisposition for SLE in Asian populations.