支气管哮喘患儿亚甲基四氢叶酸还原酶基因多态性与血清免疫球蛋白E的关系

Relationship between Methylene Tetrahydrofolate Reductase Gene Polymorphism and Serum Immunoglobulin E in Bronchial Asthmatic Children

目的探讨支气管哮喘(哮喘)患儿亚甲基四氢叶酸还原酶(MTHFR)基因C677位点多态性与血清IgE水平的相关性。方法选择95例哮喘患儿作为病例组,均为急性发作期或临床缓解期哮喘患儿,患病前2周均未使用过肾上腺皮质激素及免疫调节剂。另选择健康儿童113例作为健康对照组。2组儿童年龄及性别比较差异均无统计学意义。采用PCR-限制性片段长度多态性分析法对病例组和健康对照组儿童外周血白细胞MTHFR基因C677位点基因多态性进行研究,应用双抗体夹心ELISA法检测2组儿童血清总IgE水平。结果健康对照组MTHFR 677C/T的3种基因型频率分别CC 35.4%、CT 45.1%、TT 19.5%,病例组分别为CC 24.2%、CT 40.0%、TT 35.8%,677C/T基因型分布频率在哮喘病例组和健康对照组间差异有统计学意义(χ2=7.556 5,P<0.05)。病例组T等位基因的频率为55.3%,健康对照组为42.0%,病例组较健康对照组显著增高,其患哮喘的危险度是健康对照组的1.71倍(χ2=7.254 7,P<0.01;95%CI:1.13～2.57)。病例组血清总IgE水平在各基因型患儿间比较差异有统计学意义(F=3.46,P<0.05),健康对照组血清总IgE水平在各基因型儿童间比较差异无统计学意义(F=0.13,P>0.05)。结论 MTHFRC677位点C→T的基因突变增加了患儿哮喘发病的危险度,TT基因型与哮喘的发生直接相关;哮喘患儿血清总IgE水平升高,该位点基因型并非导致血清总IgE水平升高的直接原因。

Objective To explore the relationship between methylene tetrahydrofolate reduetase （MTHFR）gene polymorphism caused by the point mutation of eDNA 677 C and serum IgE in bronchial asthmatic children. Methods In the research,95 bronchial asthmatic children who were in acute exacerbation or clinical remission were chosen as asthma group,and neither adrenoeorticotropie hormone nor immuno- modulator were given to them in 2 weeks before they went to hospital;113 healthy children were chosen as healthy control group. There were no significant differences in age and sex between the 2 groups. Polymerase chain reaction and restriction fragment length polymorphism was used to detect MTHFR gene polymorphism. The total levels of serum IgE of the children in both groups were assayed by enzyme linked immu- nosorbent assay. Results At the site of 677,the frequencies of the 3 genotypes were found to be CC 35.4% ,CT 45.1% and TY 19.5% in the healthy control group. But in asthma group,the frequencies were CC 24.2% , CT 40.0% and TT 35.8%. There was a significant difference in the frequency distribution of allele C / T between asthma group and healthy control group （X2 = 7. 556 5 ,P 〈 0.05 ）. The frequency of alle- lic T was 55.3 % in asthma group, and 42.0% in healthy control group, and the frequency of allelic T in asthmatic children was significantly higher than that in healthy control group. The OR for the asthmatic children compared with healthy children was 1.71 （X2 = 7. 254 7, P 〈 0.01 ;95% CI： 1.13 -2.57 ）. The difference of the total levels of serum IgE between different genotypes in asthma group was significant （F=3.46,P〈0.05） ;but the difference in healthy control group was not significant （F=0.13,P〉0.05）. Conclusions cDNA 677 T allele of MTHFR gene increased the risk in pathogenesis of asthmatic children. The TT genotype was a direct risk factor for asthmatic children. And the genotype may not be the direct reason of the rise in the total levels of serum IgE.