Identification of Genes for High IgE responsiveness in Chromosomes 5q31 and 11q13

(1)在IgE Fc区高亲和力受体启动子区-109位点发现一个新的单核苷酸多态性，即C → T突变，该多态性在哮喘患者和健康对照组中的分布无显著性差异。然而，T等位基因纯合子哮喘患者血清总IgE水平显著高于其他基因型（TC或CC）。当考虑到哮喘发作时的年龄时，多态性对血清总IgE的影响变得更加明显（p=0.0004）。(2)我们还在IL-4基因的非翻译区发现了一种新的多态性（+33 C/T）。哮喘组和健康对照组T等位基因频率分别为0.675和0.671，两组间差异无统计学意义。同时，在所有研究对象或哮喘患者中，CT或CC基因型个体的血清总IgE水平显著更高，即使在校正性别后也是如此 关于我们 与CC基因型的年龄比较。(3)我们分析了上述两种单核苷酸多态性（SNP）对血清总IgE水平的相互作用。这两个SNP在哮喘患者中的作用似乎依赖于每个SNP的基因型。(4)我们发现特应性皮炎患者和健康对照组之间上述两个SNP的频率没有显著差异，因此表明这些基因多态性对疾病的发展没有贡献。此外，这两个SNP与特应性皮炎患者的血清总IgE水平无关。因此，我们得出结论，基因多态性或环境因素以外的高亲和力IgE Fc受体或IL-4的基因有更大的影响个体间差异，血清总IgE水平升高的特应性皮炎患者。(5)我们已经发现，在位置287和1353下游的毒蕈碱受体M1基因的翻译起始位点的氨基酸变化的SNP。病例对照研究发现，哮喘患者CC基因型频率显著高于健康对照，提示M1受体基因可能独立于特应性而影响哮喘的发生。少

(1) We found a C to T change, novel single nucleotide polymorphism at position -109 in the promoter region of high affinity receptor for Fc portion of IgE.There was no significant difference in the distribution of this polymorphism between patients with asthma and healthy controls. However, asthmatic patients homozygous for allele T had significantly higher total serum IgE levels (p=0.0015) than those with other genotypes (TC or CC). When ages at asthma onset were taken into account, the effects polymorphism on serum total IgE became more evident (p=0.0004).(2) We have also found a novel polymorphism (+33C/T) in the untranslated region of the IL-4 gene. The allele frequencies of T in asthmatic patients and healthy controls were 0.675 and 0.671, respectively, and there was no significant difference between the two groups. Meanwhile, individuals with genotype CT or CC in all study subjects or asthmatic patients had significantly higher serum total IgE levels, even when corrected for sex … More and ages compared with those with genotype CC.(3) We analyzed the interaction of two aforementioned single nucleotide polymorphisms (SNP) on serum total IgE levels. The effects of the two SNP in asthmatic patients seemed to be dependent on genotypes of each SNP.(4) We found no significant differences in the frequencies of two aforementioned SNP between patients with atopic dermatitis and healthy controls, thus indicating that these gene polymorphisms did not contribute to the development of the disease. Also, the two SNP did not correlate with serum total IgE levels in patients with atopic dermatitis. Therefore, we concluded that gene polymorphisms or environmental factors other than genes for high affinity IgE Fc receptor or IL-4 had greater impact on the interindividual differences in increased levels of serum total IgE in patients with atopic dermatitis.(5) We have found SNPs without amino acid changes at positions 287 and 1353 downstream from a translation initiation site of the muscarinic receptor M1 gene. A case-control study on the polymorphisms revealed that the frequency of genotype CC in patients with asthma was significantly higher than healthy controls, thus suggesting that M1 receptor gene may affect the occurrence of asthma independently of atopy. Less