根據(jù)紐約路透社的報(bào)導(dǎo),，挪威的科學(xué)家發(fā)現(xiàn)嗜伊紅性白血球陽離子蛋白 (eosinophil cationic protein, ECP)基因，也就是RNASE3基因,，其單點(diǎn)核酸變異(Single Nucleotide Polymorphism; SNP)可能與氣喘(asthma)以及血清嗜酸性粒細(xì)胞陽離子蛋白改變量(serum eosinophil cationic protein levels,，s-ECP)有關(guān)，此研究發(fā)表于四月份的Allergy期刊,。
挪威奧斯陸Ulleval綜合醫(yī)院的Monica Cheung Munthe-Kaas博士表示：「s-ECP是發(fā)炎反應(yīng)的一個(gè)血清指標(biāo),，在針對(duì)ECP基因的研究中，發(fā)現(xiàn)RNASE3的基因變異與氣喘患者的s-ECP量的改變有關(guān)聯(lián)性,?！寡芯咳藛T調(diào)查了來自于挪威及荷蘭的177個(gè)家庭，發(fā)現(xiàn)在RNASE3基因中有三點(diǎn)單點(diǎn)核酸突變與氣喘及s-ECP含量有密切關(guān)系,，核酸的突變及其位置分別位于-38CA, +371CG以及+499CG,。突變后的基因會(huì)導(dǎo)致過敏性氣喘、s-ECP以及s-IgE升高，也會(huì)導(dǎo)致支氣管高反應(yīng)性(bronchial hyperresponsiveness,，BHR)等現(xiàn)象,。
（編譯/陳瑞娟） (資料來源 : Bio.com)
原始出處:
Allergy，Volume 62 Issue 4 Page 429 - April 2007
To cite this article: M. C. Munthe-Kaas, J. Gerritsen, K. H. Carlsen, D. Undlien, T. Egeland, B. Skinningsrud, T. Tørres, K. L. Carlsen (2007)
Eosinophil cationic protein (ECP) polymorphisms and association with asthma, s-ECP levels and related phenotypes
Allergy 62 (4), 429–436.
doi:10.1111/j.1398-9995.2007.01327.x
Eosinophil cationic protein (ECP) polymorphisms and association with asthma, s-ECP levels and related phenotypes
M. C. Munthe-Kaas1,21Department of Pediatrics, Ullevål University Hospital, Oslo, Norway2Institute of Medical Genetics, Ullevål University Hospital, University of Oslo, Oslo, Norway,
1Department of Pediatrics, Ullevål University Hospital, Oslo, Norway; 2Institute of Medical Genetics, Ullevål University Hospital, University of Oslo, Oslo, Norway; 3University Medical Centre Groningen, Department of Pediatrics, University of Groningen, Groningen, The Netherlands; 4Faculty of Medicine, University of Oslo, Oslo, Norway; 5Voksentoppen, Department of Pediatrics, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway; 6Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway
Monica Cheng Munthe-Kaas
Department of Pediatrics
Ullevål University Hospital
N-0407 Oslo
Norway
The study was performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the lung and environment), a member of the GA2LEN (Global Asthma and Allergy European Network).
ECP, eosinophil cationic protein; BHR, bronchial hyperresponsiveness; GATA-1, globin transcription factor-1; GAIN, Genetics of Asthma International Network; ICS, inhaled corticosteroids; NFAT, nuclear factor of activated T-cells; SNP, single-nucleotide polymorphism; SPT, skin-prick test; TDT, transmission disequilibrium test; UTR, untranslated region
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
