Associations of toll-like receptor polymorphisms with systemic lupus erythematosus: A meta-analysis.

OBJECTIVE: The objective of this study was to examine whether polymorphisms in toll-like receptors 7 and 4 (TLR7 and 4) contribute to vulnerability to systemic lupus erythematosus (SLE).

METHODS: We searched MEDLINE, Embase, and Web of Science for relevant articles and performed a meta-analysis to investigate the relationship between TLR7 rs179008, rs3853839, rs1790010, TLR4 rs4986791, and rs798690 polymorphisms and SLE.

RESULTS: Eighteen studies and 16 papers including 8022 patients with SLE and 9822 healthy controls were retrieved. Meta-analysis revealed that the TLR7 rs179008 T variant was not associated with SLE (OR = 1.008, 95% CI = 0.849-1.394, P = 0.504). Ethnic classification revealed no association between the TLR7 rs179008 T gene and SLE in either European or Latin American groups. Additionally, homozygous comparison, recessive, and dominant models revealed no association between the TLR7 rs179008 variant and SLE. In contrast, a significant association between SLE and the TLR7 rsrs3853839 GG + GA allele (OR = 2.135, 95% CI = 1.502-3.035, <0.001; OR = 23.20, 95% CI = 14.13-38.08, <0.001) was observed in the Arab and Asian groups. The T variant of TLR7 rsrs179010 was also associated with SLE in Asians (OR = 1.177, 95% CI = 1.048-1.321, P = 0.006). In contrast, the TLR4 rs4986791 variant was not associated with SLE in Europeans when allele, homozygous comparison, recessive, and dominant models were used. Furthermore, no association between the TLR4 rs4986790 variant and SLE risk in Europeans was found using any genomic model.

CONCLUSIONS: Meta-analysis revealed that the TLR7 rs3853839 variant is associated with SLE risk in Asians and Arabs and that TLR7 rs179010 is associated with SLE in Asians. However, TLR7 rs179008, TLR4 rs4986791, and TLR rs798690 polymorphisms were not associated with SLE risk.