RRC ID 37689
Author Kawai T, Takeshita S, Imoto Y, Matsumoto Y, Sakashita M, Suzuki D, Shibasaki M, Tamari M, Hirota T, Arinami T, Fujieda S, Noguchi E.
Title Associations between decay-accelerating factor polymorphisms and allergic respiratory diseases.
Journal Clin Exp Allergy
Abstract BACKGROUND:Allergic diseases such as asthma and allergic rhinitis are major causes of morbidity in developed countries. The pathology underlying allergic respiratory diseases is considered to be IgE-mediated type I allergy characterized by mucosal inflammation that occurs in response to allergen exposure. They are common diseases involving a complex inheritance. Complement systems are known to play an important role in allergic diseases. Decay-accelerating factor (DAF) is important for the regulation of the complement system and is a good candidate for determining the susceptibility to allergic diseases.
OBJECTIVE:The present study aimed to investigate whether polymorphisms in the DAF gene are associated with allergic respiratory diseases in the Japanese population.
METHODS:We performed mutation screenings of DAF and conducted a tag single-nucleotide polymorphisms (SNP) association analysis for 684 unrelated adult individuals with seasonal allergic rhinitis (SAR) with Japanese ceder pollen, 188 mite-sensitive adults with asthma, and 346 unrelated non-allergic healthy controls.
RESULTS:DAF is located in the tight linkage disequilibrium (LD) block spanning 62 kb. The tag SNP analysis revealed that rs10746463 was significantly associated with SAR (P=0.00033) and mite-sensitive adult asthma (P=0.044). The rs2564978 and rs3841376 haplotypes, which are located in the promoter region of DAF, were in complete LD with rs10746463 (r2=1). Luciferase reporter assays with constructs containing the 5' flanking regions of DAF showed that the plasmid with rs2564978 C/rs3841376 deletion (the risk haplotype) had a statistically significantly lower transcriptional activity than that containing the rs2564978 T/rs3841376 insertion.
CONCLUSIONS:Our results suggest that DAF is one of the genes involved in conferring susceptibility to allergic respiratory diseases and show that decreased levels of DAF may be associated with the enhanced specific IgE responses occurring in allergic diseases in the Japanese population.
Volume 39(10)
Pages 1508-14
Published 2009-10-1
DOI 10.1111/j.1365-2222.2009.03316.x
PII CEA3316
PMID 19681921
MeSH Adult Aged Asian People Asthma / genetics* Asthma / metabolism CD55 Antigens / genetics* CD55 Antigens / metabolism Female Genetic Predisposition to Disease* Haplotypes / genetics Humans Immunoglobulin E / metabolism Japan Linkage Disequilibrium / genetics* Male Middle Aged Polymorphism, Single Nucleotide* Rhinitis, Allergic, Seasonal / genetics* Rhinitis, Allergic, Seasonal / metabolism
IF 4.217
Times Cited 10
WOS Category ALLERGY IMMUNOLOGY
Resource
Human and Animal Cells A549(RCB0098)