Munthe-Kaas M C, Gerritsen J, Carlsen K H, Undlien D, Egeland T, Skinningsrud B, Tørres T, Carlsen K L
Department of Pediatrics, Ullevål University Hospital, Oslo, Norway.
Allergy. 2007 Apr;62(4):429-36. doi: 10.1111/j.1398-9995.2007.01327.x.
Eosinophil cationic protein (ECP) is a potent cytotoxic secretory protein with bactericidal and antiviral properties. ECP is released by activated eosinophils and regarded as a marker of eosinophilic inflammation. High levels of ECP have been reported in cases of active asthma and other allergic diseases. This study aimed to assess whether three single-nucleotide polymorphisms (SNPs) in the ECP gene (RNASE3) on chromosome 14 q24-q31 or their haplotypes are associated with asthma, allergy, or related phenotypes.
The three SNPs -38CA, +371CG and +499CG in RNASE3 and their haplotypes were analyzed for associations with asthma, serum-ECP (s-ECP) levels, allergic sensitization (positive skin-prick test to common allergens), bronchial hyperresponsiveness (BHR) assessed by methacholine inhalation, and serum-IgE (s-IgE) levels in 177 families from Norway and the Netherlands identified through siblings with asthma.
Transmission disequilibrium test (TDT) demonstrated significant associations between the A-G-G haplotype and asthma as well as the specific phenotypes allergic asthma (but not non-allergic asthma), high s-ECP, high s-IgE and BHR, while the C-G-G haplotype was associated with reduced occurrence of these traits. In addition, the -38A allele was associated with high s-ECP levels and allergic asthma.
The present study suggests that the A-G-G haplotype in the RNASE3 gene influences the development of asthma, in particular, an allergic form of asthma. Furthermore, as the -38CA SNP lies in close vicinity of known intron-regulatory sites, results of SNP analysis suggest that the detected association is possibly linked to a genetic transcriptional control of s-ECP levels.
嗜酸性粒细胞阳离子蛋白（ECP）是一种具有杀菌和抗病毒特性的强效细胞毒性分泌蛋白。ECP由活化的嗜酸性粒细胞释放，被视为嗜酸性粒细胞炎症的标志物。在活动性哮喘和其他过敏性疾病病例中，已报道ECP水平较高。本研究旨在评估14号染色体q24 - q31上ECP基因（RNASE3）中的三个单核苷酸多态性（SNP）及其单倍型是否与哮喘、过敏或相关表型有关。
分析RNASE3中的三个SNP（-38CA、+371CG和+499CG）及其单倍型与哮喘、血清ECP（s-ECP）水平、过敏致敏（对常见变应原皮肤点刺试验阳性）、通过吸入乙酰甲胆碱评估的支气管高反应性（BHR）以及来自挪威和荷兰的177个家庭中血清IgE（s-IgE）水平的关联，这些家庭是通过患有哮喘的兄弟姐妹确定的。
传递不平衡检验（TDT）表明，A-G-G单倍型与哮喘以及特定表型过敏性哮喘（而非非过敏性哮喘）、高s-ECP、高s-IgE和BHR之间存在显著关联，而C-G-G单倍型与这些特征的发生率降低有关。此外，-38A等位基因与高s-ECP水平和过敏性哮喘有关。
本研究表明，RNASE3基因中的A-G-G单倍型影响哮喘的发生发展，尤其是过敏性哮喘形式。此外，由于-38CA SNP位于已知内含子调控位点附近，SNP分析结果表明检测到的关联可能与s-ECP水平的基因转录控制有关。
