The Correlation Between Thromboxane A₂ Receptor Gene Polymorphism And Susceptibility Of Asthma

Objective:To determine whether the thromboxane A₂ receptor gene T924C polymorphism is associated with the hereditary susceptibility of asthma as well as the change in lung function and serum specific IgE in Han nationality children from Tianjin of China.Through this study,we can find the cause of asthma from molecular genetics;It is very effective for the early diagnosis and intervention.Methods:This study recruited 125 children who were suffering from asthma acute episode and 49 healthy children as control group.Polymerase chain reactions-Restriction fragment length polymorphism(PCR-RELP)techniques and electrophoresis on agarose were used to detect the TBXA₂R SNP.RSV IgM and IgG were measured by ELISA.In asthma group,serum consertrations of specific IgE antibodies were measured by Allergyscreen.All asthmatic patients who are more than five years old underwent spirometric assessment.Results:1.Compare the age between asthmatic patients and control group using t-test,there is no significant difference between the two groups(t=0.703,p=0.438).2.Compare the gender between asthmatic patients and control group using x²-test, There is no significant difference between the two groups(x²=0.454,p=0.500).3.The distribution frequencies of genotypes(TT,TC,C,C)in asthmatic patients were 67,52,6 respectively,the theoretical values were 69,47,8,compared by x²-test, x²=0.564,p=0.754;and the corresponding figures in controls were x²=0.1470, p=0.479.There is no significant difference in the two groups.4.The distribution frequencies of genotypes(TT,TC,CC)in asthmatic patients were 67,52,6,and the corresponding figures in controls were 38,7,4,compared by x² -test,x²=11.784,p=0.003,there is significant difference.The frequencies for wild-type(T)and mutant alleles(C)in T924C in our asthmatic patients were 0.744 and 0.256 respectively,and the corresponding figures in controls were 0.8469 and 0.1531,compared by x²-test,x²=4.251,p=0.039.The C alleles frequencies in asthmatic patients are obviously higher than in controls.5.The asthmatic patients were divided in two groups(≥3 years of age and＜3 years of age).Compare the genotypes and alleles frequencies in two grups using x² -test,the results were respectively,x²=0.547(p=0.761),x² =0.404(p=0.525), there is no significant difference.6.The heterozygous genotype(TC)can significantly increase the risk of developing asthma,the OR value(95%CI)is 4.213(1.741-10.196),p=0.001.The OR(95% CI)value of homozygous mutant genotype(CC)is 0.851(0.226-3.205),p=0.811, there is no statistically significance.7.Compare the genotypes and alleles frequencies between simple asthmatic patients and asthma coexisting other anaphylaxis patients using x²-test.The results were respectively x²=0.245(p=0.620),x²=0.384(p=0.535),there is no statistically significance;the corresponding figures between simple asthmatic patients and asthma coexisting family history patients were x²=0.195(p=0.659),x²=0.000 (p=0.985),there is no statistically significance also.8.RSV specific antibody were positive in 57 asthmatic patients(45.6%,57/125)and 8 controls(16.33%,8/49),compare positive ratio between two groups using x ²-test,x²=12.890,p=0.000.There is significant difference.RSV specific antibody positive ratio were 31.4%(27/86)in≥3 years of age asthmatic group and 76.92%(30/39)in＜3 years of age asthmatic group.Compare the positive ratio between two asthmatic groups,x²=22.420.p=0.000,the difference is significant.9.Test the genotypes between asthmatic patients and controls whose RSV specific antibody are positive,x²=5.346,p=0.021,that is to say the genotypes distribution is different among the two groups,the TC+CC genotypes account a higher proportion in asthmatic patients than in controls.Compare the alleles frequencies between these two groups,x²=2.660(p=0.103),there is no statistically significance.10.89 asthmatic patients had elevated serum allergen-specific IgE concentrations, occupy 76.02%(89/117).Among these 89 patients,65 patients were in the≥3 years of age group,the other 24 patients were in the＜3 years of age group,the positive ratio is 82.28%and 63.16%respectively.11.Compare the genotypes(TT,TC+CC)distribution and alleles frequencies between sensitization to house dust and no sensitization to house dust,sensitization to house dust mites and no sensitization to house dust mites,sensitization to fungi and no sensitization to fungi,sensitization to cat,and no sensitization to cat,sensitization to dog,and no sensitization to dog,,the p values are all more than 0.05,there is no statistically significance.12.Compare the different item of lung function between TT group and TC+CC group using t-test,the p values were all more than 0.05,there is no statistically significance.Conclusion:1.The age and gender were matched in asthmatic patients and controls.Analysis regarding the distribution between T924C genotypes showed that the wild-type and mutant alleles were in Hardy Weinberg equilibrium in two groups.2.TBXA₂R gene T924C polymorphism exists among Han nationality children in Tianjin of China.And it is associated with the increased genetic susceptibility of developing asthma,the C allele may be susceptibility gene for asthma.The distribution of genotypes doesn't change with age.The heterozygous genotype(TC) can increase the risk of developing asthma.3.There is no association between TBXA₂R T924C polymorphism and eczema,allergic rhinitis,wheezing family history,change in lung function and serum sIgE.4.RSV infection was one of the factors that lead to asthma acute episode,and it is also a leading cause in＜3 years of age group.The TC,CC genotypes can increase the chance of wheezing in children who were infected by RSV.