Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen
Authors: L. Cheng; T. Enomoto1; T. Hirota2; M. Shimizu; N. Takahashi2; M. Akahoshi2; A. Matsuda2; Y. Dake1; S. Doi3; K. Enomoto4; A. Yamasaki5; S. Fukuda5; X.-Q. Mao5; J. M. Hopkin6; M. Tamari2; T. Shirakawa
Source: Clinical & Experimental Allergy, Volume 34, Number 8, August 2004 , pp. 1192-1201(10)
Publisher: Blackwell Publishing
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Abstract:
Summary Background A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. Objective The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. Methods We conducted a case–control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. Results Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P=0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. Conclusion These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.Keywords: ADAM33; allergic rhinitis; Japanese cedar pollinosis; single-nucleotide polymorphism; susceptibility gene
Document Type: Research article
DOI: 10.1111/j.1365-2222.2004.02008.x
Affiliations: 1: Department of Otolaryngology, Japanese Red Cross Society Wakayama Medical Center, Wakayama, Japan, 2: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan, 3: Department of Pediatric Allergy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Osaka, Japan, 4: Department of Otolaryngology and Sensory Organ Surgery, Osaka University Medical School, Suita, Osaka, Japan and 5: Department of Health Promotion and Human Behaviour, Kyoto University Graduate School of Public Health, Kyoto, Japan, 6: Experimental Medicine Unit, The Clinical School, University of Wales Swansea, Swansea, UK
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