Association Of CYP3A5 Gene Polymorphism With Susceptibility And Clinical Characteristics Of Childhood Asthma

Objective To investigate the relationship between single nucleotide polymorphisms(SNPs)of cytochrome P450 enzyme 3A5(CYP3A5)gene rs776746 and rs15524 and the genetic susceptibility of childhood asthma,and to observe the therapeutic effect of different genotypes of asthma through lung function,exhaled nitric oxide(Fe NO)and asthma control score,so as to guide the clinical treatment of childhood asthma.Methods From October 2016 to October 2020,106 asthmatic children of Han nationality in Northeast China and 100 healthy children were enrolled in this study.The SNPs of rs776746 and rs15524 were analyzed by sequencing.The patients in the case group were given inhaled corticosteroids for 3 months.Lung function and exhaled nitric oxide(Fe NO)were measured before and after treatment,and asthma control score(C-ACT/ACT)was made after treatment.Results1.Linkage analysis of rs776746 and rs15524 of CYP3A5 gene indicated that there was complete linkage disequilibrium(D’= 1).There were three genotypes(T/T,T/C and C/C)in rs776746,and there were significant differences in wild-type and variant frequencies between the case group and the control group(F=6.409,P=0.011,OR=0.214,95%CI=0.058-0.781),but there was no significant difference in allele frequency between the case group and the control group(c2 =0.211,P= 0.646).There were A/A,A/G and G/G in rs15524.There was no significant difference in the frequency of wild-type and variant between the case group and the control group(F=0.571,P=0.450),and there was no significant difference in the frequency of allele between the case group and the control group(c2 =0.211,P=0.646).2.There was no significant difference in FEV1,FVC,PEF,FEF25,FEF50 and FEF75 between wild-type and variant CYP3A5 rs776746 and rs15524(all P> 0.05).There was no significant difference in Fe NO between rs776746 and rs15524 wild-type and variant(P>0.05).3.After treatment,the improvement rates of FEF50 and FEF75 of rs776746 locus variant were significantly higher than those of wild-type(t=-2.499,-3.256,P=0.024,0.019),the improvement rates of Fe NO of rs15524 locus variant were significantly lower than those of wild type(t=3.380,2.325,P= 0.015,0.042),and the improvement rates of Fe NO of rs15524 locus variant were also significantly lower than those of wild-type(t=0.921,P=0.037).4.The C-ACT/ACT score of rs776746 variant was significantly higher than that of wild type group(t=0.571,P=0.037).There was no significant difference between rs15524 variant and wild-type group(t=0.486,P= 0.545).Conclusion1.The rs776746 and rs15524 loci of CYP3A5 gene were in complete linkage disequilibrium.2.The rs776746 genotype of CYP3A5 gene includes T/T,T/C and C/C,which may be related to the susceptibility of asthma in children in Northeast China.The improvement rate of small airway function and Fe NO in children with variant asthma was better than that of wild-type asthma.The control of variant type was better than that of wild-type.3.The genotype of rs15524 locus of CYP3A5 gene includes A/A,A/G and G/G,which may not be the susceptible locus of asthma in children in Northeast China.The improvement rate of small airway function and Fe NO of rs15524 variant was worse than that of wild-type.