J Korean Med Sci.  2012 Apr;27(4):343-349. 10.3346/jkms.2012.27.4.343.

Potential Association of DCBLD2 Polymorphisms with Fall Rates of FEV1 by Aspirin Provocation in Korean Asthmatics

• Park TJ
• Kim JH
• Park BL
• Cheong HS
• Bae JS
• Pasaje CF
• Park JS
• Uh ST
• Kim MK
• Choi IS
• Park CS
• Shin HD

• KMID: 2157892
• DOI: http://doi.org/10.3346/jkms.2012.27.4.343

Abstract

Aspirin exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyposis and aspirin hypersensitivity. The aspirin-induced bronchospasm is mediated by mast cell and eosinophilic inflammation. Recently, it has been reported that the expression of discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is up-regulated in lung cancers and is regulated by transcription factor AP-2 alpha (TFAP2A), a component of activator protein-2 (AP-2) that is known to regulate IL-8 production in human lung fibroblasts and epithelial cells. To investigate the associations between AERD and DCBLD2 polymorphisms, 12 common variants were genotyped in 163 AERD subjects and 429 aspirin tolerant asthma (ATA) controls. Among these variants, seven SNPs (rs1371687, rs7615856, rs828621, rs828618, rs828616, rs1062196, and rs8833) and one haplotype (DCBLD2-ht1) show associations with susceptibility to AERD. In further analysis, this study reveals significant associations between the SNPs or haplotypes and the percentage of forced expiratory volume in one second (FEV1) decline following aspirin challenge using multiple linear regression analysis. Furthermore, a non-synonymous SNP rs16840208 (Asp723Asn) shows a strong association with FEV1 decline in AERD patients. Although further studies for the non-synonymous Asp723Asn variation are needed, our findings suggest that DCBLD2 could be related to FEV1-related phenotypes in asthmatics.

Keyword

DCBLD2; Aspirin Exacerbated Respiratory Diseases; Single Nucleotide Polymorphism (SNP); Haplotype

MeSH Terms

Adolescent
Adult
Aged
Alleles
Asian Continental Ancestry Group/*genetics
Aspirin/*adverse effects
Asthma, Aspirin-Induced/etiology/*genetics
Female
Forced Expiratory Volume/drug effects/genetics
Gene Frequency
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Male
Membrane Proteins/*genetics
Middle Aged
*Polymorphism, Single Nucleotide
Regression Analysis
Republic of Korea
Risk Factors
Young Adult

Figure

• 

  Fig. 1 Gene maps and haplotypes of DCBLD2. (A) Polymorphisms of DCBLD2 investigated in this study. Coding exons are marked by shaded blocks; 5'- and 3'-untranslated region (UTR) by white blocks. Two SNPs (rs7615856 and rs828621) are in complete LD (r2 = 1). (B) Haplotypes of DCBLD2 in the Korean population. Only those with frequencies over 0.05 are analyzed for associations. (C) LD blocks and correlation coefficients among DCBLD2 polymorphisms.

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