Association of polymorphism of C159T gene of receptor CD14 and antiendotoxin immunity in patients with refractory / corticosteroids-sensitive asthma
Keywords:
bronchial asthma, endotoxin, C159T polymorphism of CD14Abstract
Introduction. Therefractory asthma refers to the phenotype, which is characterized by severe persistent course with frequent exacerbations and resistance to corticosteroid therapy. This phenotype of asthma can be related to C159T polymorphism of CD14 receptor gene
Material and methods.There were studied the C159T polymorphism of CD14 gene in 331 patients with bronchial asthma. The control group consisted of 285 healthy individuals of Crimea. The C159T gene polymorphism of CD14 was detected by allele-specific polymerase chain reaction with electrophoretic detection. The distribution of genotypes was checked according to the law of the Hardy-Weinberg equilibrium by using Fisher's exact test and χ2. There was used logistic regression to determine the difference in the frequency of genotypes and alleles.
Results and discussion. In our study have been identified 291 patients with corticosteroid-sensitive and 40 with refractory asthma. The genotype distribution of control (CC – 34%, CT – 51%, CT – 15%) and patients with corticosteroid-sensitive asthma (CC – 29%, CT – 53%, CT – 18%) were in accordance with the law of Hardy-Weinberg equilibrium and did not significantly differ (χ2 = 2.204, P = 0.332). There were no significant differences when comparing the allele and genotype frequencies by using risk allele T and C model.In the control group the frequency distribution of genotypes CC – 34%, CT – 51%, TT – 15% did not differ significantly (χ2 = 3.540, P = 0.170) from refractory asthma (CC – 52%, CT – 35%, CT – 13%). The risk analysis for the T allele showed that the frequency of CT+TT genotype in patients with refractory asthma (49%) was significantly lower (OR = 0.467, CI = [0.240-0.910], χ2 = 5.17, p = 0.023) compere to control (66 %). In turn, the difference of allelic frequencies for the control and patients with persistent asthma did not differ significantly (p = 0.076).The content of anti-endotoxin antibody of class A in patients with corticosteroid-sensitive asthma in serum and induced sputum did not differ significantly (p> 0.05) from control. The anti-ET-IgM was significantly higher (<0.001) in the control group for all genotypes, while genotype TT contents of this immunoglobulin was significantly higher (p <0.05) compare to CC genotype. The concentration of anti-ET-IgG for the studied genotypes was significantly higher (p <0.05) compare to the control group. Patients with TT genotype had the highest content of sCD14 in serum and induced sputum, which was significantly different (p <0,05) compare to control values and CC+CT genotypes. Levels of Anti-ET-IgA and anti-ET-sIgA in patients with refractory asthma did not differ significantly (p> 0.05) from control group. The content of anti-ET-IgM and serum sCD14 in patients with CC and CT genotypes were significantly higher (p <0,05) compare to control and did not differ significantly (p> 0,05) for TT genotype ones. The concentration of anti-ET-IgG and sCD14 in induced sputum was significantly higher (p <0,05) compare to control, but did not differ between genotypes.
Conclusion. In a population of Crimea the risk of refractory asthma significantly reduced (OR = 0.467, CI = [0.240-0.910], p = 0.023) in the presence of CT or TT genotype of C159T polymorphism of CD14 receptor gene. The corticosteroid-sensitive asthma patients with TT genotype of CD14 receptor had high concentration of anti-endotoxin IgM and sCD14.
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