Abstract:

Objective   To evaluate the effects of polymorphisms in TLR7 and  TLR8 on asthma risk and asthma-related phenotypes in Han population of Jiangsu province of China. Methods   We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers of Han population from the same area in Jiangsu province. Genotyping of the selected SNPs, TLR7 rs5935436， TLR8 rs3761623 and rs3764880 was performed using multiplex PCR combined with tagged array single base extension technology（SNPstream）. Total IgG level in serum was determined by ELISA. We conducted case-control and case-only association studies between the selected SNPs in TLR7 and TLR8 and asthma or asthma-related phenotypes. Results   The T allele of rs5935436 SNP in TLR7 was a protective factor for males in developing asthma(adjusted OR=0.126, 95%CI=0.016-0.995, P=0.049). The G allele of the rs3761623 appeared more frequently in male asthmatics without allergic rhinitis (adjusted OR=3.782, 95% CI=1.02214.045, P=0.047), while the CT/TT genotype of the rs5935436 appeared less frequently in female asthmatics with allergic rhinitis (adjusted OR=0.180, 95%CI=0.041-0.902, P=0.037). The homozygote AA of rs3761623 and GG of rs3764880 were positively associated with lower FEV1% and asthma severity in female asthmatics. These results were confirmed by haplotype analysis. Conclusion   TLR7/8 polymorphisms may play an important role in the pathogenesis of asthma, which is gender-dependent. This could be clinically useful to identify patients at risk of asthma and prevent the occurrence of asthma.

Key words: Gene, polymorphism; Asthma; Toll-like receptors; Phenotype;Atopy; Jiangsu province； Han population