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

(1)在IgE高亲和力受体Fc部分启动子区域的-109位，我们发现了一种新的C-T突变，即单核苷酸多态。哮喘患者和健康对照组之间这种多态的分布没有显著差异。然而，T等位基因纯合子哮喘患者的血清总IgE水平显著高于其他基因型(TC或CC)的患者(P=0.0015)。考虑发病年龄后，IL-4基因非翻译区的+33C/T多态性对血清总IgE的影响更为明显(p=0.0004)。哮喘患者和健康对照组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。与此同时，在所有研究对象或哮喘患者中，携带CT或CC基因的个体的血清总免疫球蛋白水平显著更高，即使将性别…校正后也是如此分析上述两个单核苷酸多态(SNP)对血清总IgE水平的交互作用。这两个SNP在哮喘患者中的作用似乎依赖于每个SNP的基因类型。(4)我们发现上述两个SNP在特应性皮炎患者和健康对照组中的频率没有显著差异，表明这些基因多态在疾病的发生发展中没有贡献。此外，这两个SNP与特应性皮炎患者的血清总IgE水平没有相关性。因此，我们得出结论，除高亲和力IgE Fc受体或IL-4基因外，基因多态或环境因素对特应性皮炎患者血清总IgE水平升高的个体差异有更大影响。(5)我们在M受体M1基因翻译起始点下游的287和1353位没有发现氨基酸变化的SNPs。病例对照研究发现，哮喘患者CC基因频率显著高于健康对照组，提示M1受体基因可能独立于特应性而影响哮喘的发生。较少

(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