Abstract:

Objective

To investigate the role of the Toll-like receptor 2/9 (TLR2/9) single nucleotide polymorphisms(SNPs) in conferring susceptibility to the ANCA-associated vasculitis (AAV).

Methods

A retrospective grouped case-control design was applied. Matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to genotype the SNPs of TLR2/9 in 176 Chinese Han patients with AAV [100 cases of granulomatosis with polyangiitis (GPA), 76 cases of microscopic polyangitis (MPA)] and 485 ethnically matched healthy controls randomly collected in inpatient/outpatient department of Beijing Union Medical College Hospital from November 2011 to December 2012. The allele and genotype frequencies were used for association analysis. The distributions of genotype frequencies in each group were compared and haplotype frequencies were analyzed.

Results

A synonymous SNPs in the exon of TLR2 (rs3804100) was closely associated with the risk of MPA, and the frequencies of allele C in MPA patients and healthy controls were 39.5%(60/76) and 27.9%(271/485), respectively (Pc=0.026, OR1.68,95%CI 1.18-2.40). But the frequency of allele C in GPA patients was 26.5%(53/100) and was not associated with GPA (χ²=0.17, Pc＞0.05). Haplotype analysis showed CC haplotype frequencies in the region of 2 MPA groups were significantly higher than in the control group [39.5%(60/76) vs 27.6%(134/485)], and the differences were statistically significant (χ²=8.74, Pc=0.022). Also, there were no significant differences in the distribution of two TLR9 SNPs(rs352139, rs187084) between patients and healthy controls (χ²=0.29, 0.05, all of Pc＞0.05 respectively).

Conclusion

These results suggested that rs3804100 (TLR2) is closely associated with MPA but not GPA for the first time, while TLR9 SNPs (rs352139, rs187084) may be not associated with AAV, GPA or MPA.

Key words: Antineutrophil cytoplasmic autoantibodies-associated vasculitides, Polymorphisms,single nucleotide, Toll like receptor