Polymorphisms of TLR7 and TLR8 associated with risk of asthma and asthma-related phenotypes in a southeastern Chinese Han population

Objective： To evaluate the effects of polymorphisms in TLR7 and TLRS（as potential candidate genes） on asthma risk and asthma-related phenotypes. Methods： We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers from the same area of southeast China. Genotyping of each selected SNP was performed using multiplex PCR in conjunction with tagged array single base extension technology. 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 protective from developing asthma in males （adjusted ORs = 0.126, 95% CIs = 0.016-0.995）. The CT/TT genotype of rs5935436 was less frequent in female asthmatics with allergic rhinitis （adjusted ORs = 0.18, 95% CIs = 0.04-0.90）. 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 and TLR8 polymorphisms may play an important role in the pathogenesis of asthma that is gender-dependent. This could be clinically useful, both for identifying patients at risk of asthma and for preventing its occurrence.

Gene transfer of a β_2-adrenergic receptor kinase inhibitor up-regulates the level of β_2-adrenergic receptor and cAMP in the asthmatic murine lung

Objective： To investigate the effects of gene transfer of a β-adrenergic receptor（β-AR） kinase inhibitor（β ARIct） on pulmonary β2-adrenergic receptor and cAMP following β2-AR agonist treatment in asthmatic mice, and to analyze the relationship between the routes of gene delivery and the changes of β2AR and cAMP. Methods： BALB/c mice were sensitized and challenged by ovalbumin to establish the asthmatic model treated with βAR agonist （salbutamol injected intramuscularly）. The plasmid with the expression of βARKct was constructed and βARKct gene transfer was performed through intravenous injection or intratracheal instillation in asthmatic mice. The gene expression was measured with Western blot analysis, and the changes of pulmonary β-AR and cAMP evaluated by Radioimmunoassay. Results： The expression of tranfered βARKct gene was detectable in lungs and it was expressed more in the lungs of the mice receiving intratracheally plasmid than those receiving intravenously. The levels of βAR and cAMP were upregulated after using plasmid-βARKct to the asthmatic mice treated with βAR agonist. Conclusion： Our results indicated that there were down-regulation of βAR and cAMP in asthmatic mice treated with βAR agonist. Gene transfer of βARKct could inhibit the extent of the down-regulation of βAR and cAMP. The route of gene delivery could also affect the degree of up-regulation of βAR and cAMP. Gene transfer βARKct may provide a novel approach to the therapeutic strategy for asthma.