A polymorphism* in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E
A polymorphism* in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E
复制标题
DOI：
10.1165/ajrcmb.20.5.3494
复制
发表时间：
1999-05-01
影响因子：
6.4
通讯作者：
Martinez, FD
中科院分区：
文献类型：
--
作者：
Baldini, M;Lohman, IC;Martinez, FD
总血清免疫球蛋白（IG）E水平受遗传调节，但遗传机制尚不清楚。由辅助性T细胞（Th）1和Th 2淋巴细胞产生的细胞因子控制IgE合成。细菌抗原可能有利于Th 1细胞从幼稚CD 4阳性T细胞通过CD 14依赖性途径的发展。CD 14在单核细胞和巨噬细胞的表面上组成性表达，并且也以可溶性形式（sCD 14）存在于血清中。CD 14基因定位于染色体5q131.1，这是调节血清总IgE基因座的候选区域。我们假设CD 14基因的遗传变异可能影响Th细胞分化，从而影响血清总IgE。我们鉴定了从主要转录起始位点（CD 14/-159）的碱基对-159处的C到T转变。在481名儿童中，等位基因C的频率为51.4%。TT纯合子sCD 14水平显著高于CC和CT基因型携带者（P = 0.0 1）。TT纯合子也有显着较低的IgE水平比其他两种基因型的载体，但差异显着，只有在儿童皮肤试验阳性，当地的空气过敏原（P = 0.004）。CD 14/-159与外周血单个核细胞的白细胞介素（IL）-4或干扰素（IFN）-γ应答之间没有关联。然而，IFN-γ和IL-4应答分别与血清sCD 14水平呈正相关和负相关。结论CD 14/-159在调节血清sCD 14水平和血清总IgE水平中起重要作用。
Total serum immunoglobulin (Ig)E levels are genetically regulated, but the mechanism of inheritance is not well understood. Cytokines produced by T-helper (Th)1 and Th2 lymphocytes control IgE synthesis. Bacterial antigens may favor the development of Th1 cells from naive CD4-positive T cells through a CD14-dependent pathway. CD14 is constitutively expressed on the surface of monocytes and macrophages, and is also present in serum in a soluble form (sCD14). The CD14 gene maps to chromosome 5q131.1, a candidate region for loci regulating total serum IgE. We hypothesized that genetic variants in the CD14 gene could influence Th-cell differentiation and thus total serum IgE. We identified a C-to-T transition at base pair - 159 from the major transcription start site (CD14/-159). Among 481 children recruited from a general population sample, frequency of allele C was 51.4%. TT homozygotes had significantly higher sCD 14 levels than did carriers of both the CC and CT genotypes (P = 0.01). TT homozygotes also had significantly lower levels of IgE than did carriers of the other two genotypes, but differences were significant only among children who were skin test-positive to local aeroallergens (P = 0.004). There was no association between CD14/-159 and either interleukin (IL)-4 or interferon (IFN)-gamma responses by peripheral blood mononuclear cells. However, IFN-gamma and IL-4 responses were positively and negatively correlated, respectively, with serum sCD 14 levels. We conclude that CD14/-159 plays a significant role in regulating serum sCD14 levels and total serum IgE levels.