Subfamily. TLR2 And IL-17F Genetic Polymorphism And High-sensitivity C-reactive Protein And Bronchial Asthma Relationship

Part 1 High sensitivity C-reactive protein:a predicative marker in severe asthmaBackground and objective:Serum levels of high-sensitivity C-reactive protein(hs-CRP)are associated with asthma allowing for the evaluation of clinical inflammation,but the relationship between higher levels of hs-CRP and severe asthma remains unclear.This study aimed to investigate whether hs-CRP is associated with asthma severity and clinical variables(pulmonary function,total serum IgE,and peripheral blood eosinophil counts).Methods:The hs-CRP and clinical variables were determined among 177 control subjects and 281 asthmatic patients(84 intermittent, 30 mild,63 moderate and 104 severe).Results:hs-CRP was examined as continuous and quartiles variables(＜0.23,0.23-0.51,0.51-1.42,and≥1.42 mg/L)among five groups.The logistic regression analysis revealed the serum hs-CRP levels, as a continuous variable,were associated with an increased risk of the asthmatic patients[adjusted odds ratios(OR)=1.15,95%confidence intervals(CI)=1.02-1.30,P=0.021]and the severe asthmatic patients (adjusted OR=1.90,95%CI=1.47-2.46,P=0.006).As compared with the subjects in the lower quartile of hs-CRP(＜0.23 mg/L),subjects in the highest quartile(≥1.42 mg/L)had a significant increased risk of asthma after adjustment for age,gender,smoking,ICS and BMI.Of note,after subdivided into 4 stages,patients with higher quartiles were at increased risk for severe asthma(adjusted OR=3.81,95%CI=1.51-9.58,P=0.004 for the 3rd quartile;adjusted OR=9.8,95%CI=3.99-24.06 P＜0.0001for 4th quartile,respectively),a significant dose-response effect on severe asthma risk was observed(trend test:x~2=23.23,P＜0.001).However,no association was detected between hs-CRP and the non-severe asthmatic groups.Conclusions:These findings suggest that hs-CRP might be a potential surrogate marker of risk factors of asthma severity in adult, which is promising for future management and prevention of asthma.Part 2 Putative association of polymorphisms in Toll-like receptor 2 subfamily and IL-17F genes with adult asthma in southeastern ChineseBackground:Cell activation through Toll-like receptors(TLRs)and IL-17 family has robust effects on host immunity and the pathogenesis of asthma.TLR2 subfamily is a pivotal member of the TLR family,IL-17F, a member of the IL-17 cytokine family and one of the key cytokines regulating the expression of airway inflammation.This study aimed to investigate the relationship between genetic variations in TLR2 subfamily and IL-17F and asthma in southeastern Chinese.Methods:Ten single nucleotide polymorphisms(SNPs)in TLR2 subfamily genes(TLR1,2,6 and 10)and IL-17F were genotyped in 318 asthmatics and 352 controls using GenomeLab SNPstream genotyping system.Both single marker and haplotype associations were analyzed.Results:1)In the single locus analyses,the polymorphism of rs763780/IL-17F achieved significant differences in the genotype distributions between the cases and the controls(the Fisher exact test P =0.0142).The logistic regression analyses revealed that TLR2 rs7656411 variant homozygote(TT)was associated with a significantly reduced risk of asthma(adjusted OR=0.63,95%CI=0.41-0.98,P=0.041),the combined enotypes(GT+TT)were associated with a non-significantly decreased risk(adjusted OR=0.77,95%CI=0.54-1.09,P≥0.05),when compared with wild homozygote(GG).Heterozygote of the rs763780/IL-17F variant was positivly associated with asthma,the adjusted odds ratio(95%CI)for asthma was 1.58(1.06-2.36)for the rs763780/IL-17F heterozygote compared with the wild-type homozygote (P=0.0148).2)When we combined these loci and carried out the haplotype inference,three possible haplotypes of IL-17F were derived from their known genotypes.Among them,haplotype(AC)represented 12.11 of the chromosomes for cases and 8.12%of that for controls,and the haplotype distribution between the cases and the controls was statistically different(the Fisher exact test P＜0.001).Compared with the other haplotypes,the AC was associated with a increased risk of asthma (adjusted OR=1.62,95%CI=1.11-2.35,P=0.0115).3)A positive association was observed between the T allele of rs2381289 in TLR6 and allergic rhinitis in asthma(OR=1.79,95%CI=1.10-2.91,P=0.025),but the A allele of rs11466651 in TLR10 was negatively associated with allergic rhinitis(OR=0.49,95%CI=0.26-0.95,P=0.046).the increased risk associated with the rs763780/ IL-17F heterozygote was more pronounced in subjects who were men(OR=1.79,95%CI=1.06-3.05), subjects in the higher of Log-IgE(≥1.85IU/ml)(OR=1.88,95% CI=1.10-3.22,P=0.023)and subjects in the lower hs-CRP level(＜1.54 mg/L)(OR=2.57,95%CI=1.15-5.75,P=0.0218).Conclusion:These findings indicate that genetic variants in TLR2 sub-family genes and IL-17F gene may play roles in asthma susceptibility.