Gervaziev Y V, Kaznacheev V A, Gervazieva V B
V.N. Orekhovich's Institute of Biomedical Chemistry RAMS, Moscow, Russia.
Int Arch Allergy Immunol. 2006;141(3):257-64. doi: 10.1159/000095295. Epub 2006 Aug 23.
Susceptibility to the development of bronchial asthma (BA) and other atopic diseases is known to be associated with genetic components.
To evaluate the possible role of the polymorphisms in IL-4 gene promoters (C-33T, C-590T and G-1098T) in modulating allergic response and asthma in the Russian population.
The polymorphism analysis was carried out by PCR-RFLP; IL-4 and total IgE concentrations were determined by ELISA.
In the case group, the T allele was found at frequencies of 74% (C-33T), 51% (C-590T) and 5% (G-1098T); in the control group the frequencies were 22, 42 and 8%, respectively. Only the C-33T polymorphism was associated with BA. The concentrations of total IgE and serum IL-4 were raised in the case group, while in the control group they were normal. Serum IL-4 level depended on C-33T polymorphism both in the case and control groups, the mutant T allele promoting its increase. The dependence on C-590T polymorphism was detected only in the case group. As for the total IgE level, in both cases it depended on the polymorphism in the case group rather than the control. G-1098T polymorphism did not demonstrate any correlations with total IgE or serum IL-4 levels. All 3 polymorphisms did not affect the severity of BA in the case group. On the basis of the computer analysis, we propose that the T-33C region is the CREB-binding site.
Our data suggest that IL-4 promoter polymorphism in the Russian population might play a role both conferring susceptibility to BA and modulating the levels of serum IL-4 and total IgE.
已知支气管哮喘(BA)及其他特应性疾病的易感性与遗传因素有关。
评估白细胞介素-4(IL-4)基因启动子多态性(C-33T、C-590T和G-1098T)在调节俄罗斯人群过敏反应及哮喘中的可能作用。
采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)进行多态性分析;通过酶联免疫吸附测定(ELISA)法测定IL-4和总免疫球蛋白E(IgE)浓度。
病例组中,T等位基因频率分别为74%(C-33T)、51%(C-590T)和5%(G-1098T);对照组中,其频率分别为22%、42%和8%。仅C-33T多态性与BA相关。病例组中总IgE和血清IL-4浓度升高,而对照组中二者浓度正常。病例组和对照组中血清IL-4水平均取决于C-…33T多态性,突变的T等位基因促使其升高。仅在病例组中检测到对C-590T多态性的依赖性。至于总IgE水平,在两种情况下均取决于病例组而非对照组中的多态性。G-1098T多态性与总IgE或血清IL-4水平无任何相关性。所有3种多态性均不影响病例组中BA的严重程度。基于计算机分析,我们推测T-33C区域为环磷腺苷效应元件结合蛋白(CREB)结合位点。
我们的数据表明,俄罗斯人群中IL-4启动子多态性可能在赋予BA易感性以及调节血清IL-4和总IgE水平方面发挥作用。