This Article Full Text Full Text (PDF) Online Supplement Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Noguchi, E. Articles by Shibasaki, M. Search for Related Content PubMed PubMed Citation Articles by Noguchi, E. Articles by Shibasaki, M.

The Promoter Polymorphism in the Eosinophil Cationic Protein Gene and Its Influence on the Serum Eosinophil Cationic Protein Level

Departments of Medical Genetics and Immunology, Institute of Basic Medical Sciences; Department of Pediatrics, Institute of Clinical Medicine; Institute of Biological Sciences, University of Tsukuba, Tsukuba; and Akiba Hospital, Mito-City, Ibaraki, Japan

Correspondence and requests for reprints should be addressed to Emiko Noguchi, M.D., Ph.D., Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki-ken, 305-8575, Japan. E-mail: enoguchi{at}md.tsukuba.ac.jp

Asthma is characterized by reversible airway obstruction and airway inflammation. Serum levels of eosinophil cationic protein (ECP) might reflect eosinophilic airway inflammation and asthma activity. However, serum ECP levels are not elevated in some patients with asthma, even when they are symptomatic. In this study, we screened for polymorphisms in the ECP gene and analyzed association between these polymorphisms and asthma and serum ECP levels in 137 Japanese families identified through children with asthma. We identified three polymorphisms (-393C/T, -38C/A, and 124Arg/Thr) in human ECP. We did not find associations between these polymorphisms and asthma by the transmission disequilibrium test. However, we found that serum ECP levels in subjects with the -393T allele were significantly lower than those in subjects with the -393C allele. A reporter construct with the -393T allele showed significantly lower promoter activity than one with the -393C allele. Gel shift assay revealed that C/EBP proteins can bind the -393C/T polymorphic site. These data indicate that C/EBP proteins play an important role in the regulation of ECP and that a significant amount of the variance in baseline serum ECP levels may be explained by the -393C/T polymorphism. Although ECP polymorphisms are not likely to be involved in the development of asthma, measurement of ECP levels for the assessment of asthma activity may be improved when done in combination with genotyping of the -393C/T polymorphism.

Key Words: asthma • promoter • luciferase assay

This article has been cited by other articles:

				H. K. Reddel, D. R. Taylor, E. D. Bateman, L.-P. Boulet, H. A. Boushey, W. W. Busse, T. B. Casale, P. Chanez, P. L. Enright, P. G. Gibson, et al. An Official American Thoracic Society/European Respiratory Society Statement: Asthma Control and Exacerbations: Standardizing Endpoints for Clinical Asthma Trials and Clinical Practice Am. J. Respir. Crit. Care Med., July 1, 2009; 180(1): 59 - 99. [Abstract] [Full Text] [PDF]

				U.-B. Jonsson, J. Bystrom, G. Stalenheim, and P. Venge A (G->C) transversion in the 3' UTR of the human ECP (eosinophil cationic protein) gene correlates to the cellular content of ECP J. Leukoc. Biol., April 1, 2006; 79(4): 846 - 851. [Abstract] [Full Text] [PDF]

				Y.-J. KIM, V. KUMARASWAMI, E. CHOI, J. MU, D. A. FOLLMANN, P. ZIMMERMAN, and T. B. NUTMAN GENETIC POLYMORPHISMS OF EOSINOPHIL-DERIVED NEUROTOXIN AND EOSINOPHIL CATIONIC PROTEIN IN TROPICAL PULMONARY EOSINOPHILIA Am J Trop Med Hyg, July 1, 2005; 73(1): 125 - 130. [Abstract] [Full Text] [PDF]

				M. J. Tobin Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2003 Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 265 - 276. [Full Text] [PDF]